1B Cell SignallingIm

munology

B Cells Quick FactsPrimary Function

Produced in bone marrow

as naive B cells expressing

mainly IgM and IgD. Upon

activation through antigen

binding B cells differentiate

to short-living antibody-

secreting plasma cells, which eliminate circulating

infectious agents and other foreign antigens, and

memory B cells.

CD Markers (human)CD5, CD19, CD20 (B cell restricted), CD21,

CD22, CD23, CD30*, CD32, CD35, CD40,

CD45 (B220), CD47, CD48, CD66a, CD69*,

CD70*, CD72, CD79a, CD79b, CD80*, CD81,

CD86*, CD97*, CD125*, CD126*, CD152*.

*expressed on activated B cells.

Chemokine ReceptorsCCR2, CCR5, CCR6, CCR7 (CDw197), CCR8,

CXCR3 (CD183), CXCR4 (CD184), CXCR5.

Cytokine ReceptorsCD4, IL-2Rα (CD25), IL-2Rβ (CD122), IL-

4Rα (CD124), IL-5Rα (CD125), IL-6R (CD126),

IL-7R (CD127), IL-10Rα/β, IL-12Rβ1/β2, IL-

13Rα, IL-15Rα, IL-17R, IL-18Rα/β, IFN-αRI/

II, IFN-γRI/II, TNF-R1.

Cytokines Expressed by B cellsIL-5, IL-6, IL-11, IL-12, IL-13, IL-14, TNF-β.

MaturationPluripotent stem cells migrating from the bone

marrow to the spleen develop from pre-B I

lymphocytes (expressing CD10, CD19 and

CD34) to pre-B II lymphocytes (expressing CD10

and CD19, but no longer CD34) and finally to

mature B lymphocytes (expressing CD19, IgM

and IgD). In the germinal centres (GC) of the

secondary lymphoid organs IgM+IgD+ naive cells

are induced to secrete polyclonal/low affinity

antibodies, following their primary encounter with

antigen. Some of the so-activated cells will be

recruited into the GC follicles, where an antigen-

dependent education and selection begins.

Activation & SignallingAfter a B cell encounters an antigen through

binding to the B cell receptor (BCR), made up of

immunoglobulin heavy (IgH) and light (IgL) chains

associated with two signalling components, Igα(CD79a) and Igβ (CD79b), these partially

activated B cells migrate through the lymphoid

tissue. If an activated B cell encounters a T cell

that has been activated, antibodies against that

antigen are produced. If the B cell does not receive

the corresponding T cell signal, it will become

inactive (anergic) or dies through apoptosis.

For details see corresponding paragraphs.

Clinical Significance & MalignanciesDaily, the human body produces millions of

uniquely different B cells with the potential to

recognize and eliminate specific invading antigens.

As each B cell undergoes many changes in their

life cycle dependent on complex signalling

processes, B cells can also be the cause for severe

malignancies. About 85% of Non-Hodgkin’s

lymphomas are caused by B cells.

Autoimmune dieseases like systemic lupus

erythematosus (SLE) and rheumatoid arthritis are

caused by B cells which incorrectly identify certain

body cells or proteins as foreign.

MAb to CD5 (human) (UCHT2)ANC-150-020 Purified 100µg $ .00ANC-150-030 Biotin 100µg $ .00ANC-150-040 FITC 120 tests $ .00ANC-150-050 R-PE 120 tests $ .00Clone: UCHT2. Isotype: Mouse IgG21.

Immunogen: Human thymocytes / Sezary T cells.

Specificity: Recognizes epitope 2 of human CD5.

Application: FC, IHC (FS), IP.

Lit. CD5 monoclonal antibodies react with human peripheral blooddendritic cells: G.S. Wood & P.S. Freudenthal; Am. J. Pathol. 141, 789(1992)/CD5+ B cells and the immune system: P.M. Lydyard, et al.;Immunol. Lett. 38, 159 (1993)

MAb to CD19 (human) (BU12)ANC-168-020 Purified 100µg $ .00ANC-168-030 Biotin 100µg $ .00ANC-168-040 FITC 120 tests $ .00ANC-168-050 R-PE 120 tests $ .00Clone: BU12. Isotype: Mouse IgG1. Immunogen:

Human EB-4 Burkitt lymphoma cell line. Specificity:

Recognizes human CD19. Application: FC, IHC (FS),

FUNC (induces adhesion of B cells; activates B cells

resulting in inhibition or enhanced proliferation

depending on the stimulating signal).

Lit. CD19 regulation of human B cell responses. B cell proliferation andantibody secretion are inhibited or enhanced by ligation of the CD19surface glycoprotein depending on the stimulating signal used: R.E.Callard, et al.; J. Immunol. 148, 2983 (1992)/Engaging CD19 or targetof an antiproliferative antibody 1 on human B lymphocytes inducesbinding of B cells to the interfollicular stroma of human tonsils via integrinalpha 4/beta 1 and fibronectin: S. Behr and F. Schriever; J. Exp. Med.182, 1191 (1995)

Continued on Page 2

Tomorrow’s Reagents Today™Tomorrow’s Reagents Today™

CD20 - The Reliable B Cell MarkerCD20 is one of the most reliable cell surface

markers of human B lymphocytes, expressed on

all normal and most malignant B cells, with a low

rate of antibody-induced internalization. CD20 has

four membrane spanning domains and forms homo-

or hetero-tetrameric complexes that function as

Ca2+ channels that are important for normal cell

cycle progression. CD20 is constitutively

expressed with lipid rafts.

Selected Review Articles: CD20: a regulator of cell-cycle progressionof B lymphocytes: T.F. Tedder & P. Engel; Immunol. Today 15, 450(1994)/CD20-mediated apoptosis: signalling through lipid rafts: J.P.Deans, et al.; Immunology 107, 176 (2002)

MAb to CD20 (human) (2H7)ANC-169-020 Purified 100µg $ .--ANC-169-030 Biotin 100µg $ .00ANC-169-040 FITC 120 tests $ .00ANC-169-050 R-PE 120 tests $ .00Clone: 2H7. Isotype: Mouse IgG2b. Immunogen:

Human Ia-B cell line 6.16c1.3. Specificity:

Recognizes human (multimeric) CD20. Application:

FC, IHC (FS), IP, FUNC (inhibits B-lymphocyte

differentiation and induced Ig secretion; induces

apoptosis when cross-linked with a secondary

antibody).

Lit. Role of the Bp35 cell surface polypeptide in human B-cell activation:E.A. Clark, et al.; PNAS 82, 1766 (1985) /Surface phenotype and functionof tonsillar germinal center and mantle zone B cell subsets: J.A. Ledbetter& E.A. Clark; Human Immunol. 15, 30 (1986)/Association of tyrosineand serine kinases with the B cell surface antigen CD20. Induction viaCD20 of tyrosine phosphorylation and activation of phospholipase C-gamma 1 and PLC phospholipase C-gamma 2: J.P. Deans, et al.; J.Immunol. 151, 4494 (1993)/Apoptosis of malignant human B cells byligation of CD20 with monoclonal antibodies: D. Shan, et al.; Blood 91,1644 (1998)/Clustered CD20 induced apoptosis: src-family kinase,the proximal regulator of tyrosine phosphorylation, calcium influx, andcaspase 3-dependent apoptosis: J.K. Hofmeister, et al.; Blood CellsMol. Dis. 26, 133 (2000)/Alanine-170 and proline-172 are criticaldeterminants for extracellular CD20 epitopes; heterogeneity in the finespecificity of CD20 monoclonal antibodies is defined by additionalrequirements imposed by both amino acid sequence and quaternarystructure: M.J. Polyak & J.P. Deans; Blood 99, 3256 (2002)

MAb to CD20 (human) (L26)SIG-324-01 1ml $ .00Clone: L26. Isotype: Mouse IgG2a. Immunogen: B

cells derived from human tonsil. Specificity: Recognizes

human CD20. Application: IHC (PS).

MAb to CD20 (human) (MEM-97)EXB-11-217-C100 100µg $ .00Clone: MEM-97. Isotype: Mouse IgG1.

Immunogen: RAJI human Burkitt’s lymphoma cell

line. Specificity: Recognizes human CD20. Applica-

tion: FC, IP.

Lit. Supramolecular complexes of MHC class I, MHC class II, CD20,and tetraspan molecules (CD53, CD81, and CD82) at the surface of aB cell line JY: J. Szollosi, et al.; J. Immunol. 157, 2939 (1996)

MAb to B Cell Antigen 36 (human) (BLA36)SIG-319-01 1ml $ .00Clone: BLA36. Isotype: Mouse IgM. Immunogen:

Hodgkin’s Lymphoma cell line HDLM-3. Specificity:

Recognizes human B cells. Detects a 36kDa glycoprotein

present on the membrane of Reed-Sternberg cells of

Hodgkin’s Lymphoma, as well as early, activated, and

malignant B cells. Does not cross-react with T cells. The

BLA.36 monoclonal antibody is not related to other B cell

related antigens such as CD20, Ki-1, or Leu-M1. Applica-

tion: IHC (PS).

Lit. Characterization of a cellsurface molecule expressed onB-lymphocytes and Hodgkin’scells: A. Imam, et al.; CancerRes. 50, 1650 (1990)/BLA.36: aglycoprotein specificallyexpressed on the surface ofHodgkin’s and B cells: A. Imam,et al.; Anticancer Res. 10, 1095(1990)/Anti-BLA.36 monoclonalantibody shows reactivity with Hodgkin’s cells and B lymphocytes infrozen and paraffin-embedded tissues: D.R. Della Croce, et al.; Hematol.Oncol. 9, 103 (1991)

B Cell Receptor [BCR] & Co-ReceptorsThe signalling cascade initiated by antigen binding

to the B cell receptor (BCR) involves the Igα (CD79a)

and Igβ (CD79b) heterodimer which contains in its

cytoplasmic domain an immunoreceptor tyrosine-

based activation motif (ITAM). On BCR cross-linking

by multivalent antigens, BCR immediately becomes

associated with lipid rafts, where the ITAMs become

phosphorylated by the Src-family kinase Lyn,

providing a binding site for the SH2-domain-

containing kinase Syk, triggering the signalling cascades.

Activation of B cells can be enhanced by CD45, a

tyrosine phosphatase, and a co-receptor complex

consisting of CD19, CD21, CD81 and LEU13

(interferon-induced transmembrane protein 1).

Negative co-receptors are CD5, CD22, CD66a

and FcγRIIB, which contain at least one

immunoreceptor tyrosine-based inhibitory motif

(ITIM). CD72 is a B cell co-receptor that is expressed

in all stages of B cell development except plasma

cells. Ligation of CD72 enhances B cell growth and

differentiation. Recently, the class IV semaphorin,

CD100 (SEMA4D), has been identified as the natural

ligand for CD72. CD72 contains two ITIM domains

and inactivates Syk and probably Lyn. Binding of

CD100 to CD72 dephosphorylates the ITIMs, thus

enhancing B cell responses.

Selected Review Articles: Initiation and processing of signals from theB cell antigen receptor: M. Reth & J. Wienands; Annu. Rev. Immunol. 15,453 (1997)/Signal transduction from the B cell antigen-receptor: K.S.Campbell; Curr. Opin. Immunol. 11, 256 (1999)/Xid-like phenotypes: a Bcell signalosome takes shape: D.A. Fruman, et al.; Immunity 13, 1(2000)Regulation of B cell function by linker proteins: M.E. Kelly & A.C.Chan; Curr. Opin. Immunol. 12, 267 (2000)/Adapters in lymphocytesignalling: A. Leo & B. Schraven; Curr. Opin. Immunol. 13, 307 (2001)/Antigen-dependent B-cell development: A. Cariappa & S. Pillai; Curr.Opin. Immunol. 14, 241 (2002)/Lipid rafts and B-cell activation: S.K. Pierce;Nat. Rev. Immunol. 2, 96 (2002)/Regulation of B-cell signal transductionby adaptor proteins: T. Kurosaki; Nat. Rev. Immunol. 2, 354 (2002)/Regulation of B-cell fate by antigen-receptor signals: H. Niiro & E.A.Clark; Nat. Rev. Immunol. 2, 945 (2002)/Regulation of B cell fates byBCR signaling components: T. Kurosaki; Curr. Opin. Immunol. 14, 341(2002)/Semaphorins in interactions between T cells and antigen-presenting cells: H. Kikutani & A. Kumanogoh; Nat. Rev. Immunol. 3, 159(2003)/B cell inhibitory receptors and autoimmunity: N.R. Pritchard &K.G. Smith; Immunology 108, 263 (2003)

Tel: 1-800-900-0065 Fax: 1-800-900-9224 E-mail: alexis-usa@alexis-corp.com

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MAb to CD21 (human) (BU33)ANC-170-020 Purified 100µg $ .00ANC-170-030 Biotin 100µg $ .00ANC-170-040 FITC 120 tests $ .00ANC-170-050 R-PE 120 tests $ .00Clone: BU33. Isotype: Mouse IgG1. Immunogen:

Human HFB-1 cell line. Specificity: Recognizes human

CD21 (CR2). Detects a band of ~145kDa by Western

blot. Does also identify horse B cells. Application: FC,

IHC (FS), IP, WB, FUNC (inhibits binding to CD23 and

increases IgE production).

Lit. CD21 expressed on basophilic cells is involved in histamine releasetriggered by CD23 and anti-CD21 antibodies: K. Bacon, et al.; Eur. J.Immunol. 23, 2721 (1993)/Stimulation of human IgE production by asubset of anti-CD21 monoclonal antibodies: requirement of a co-signalto modulate epsilon transcripts: S. Henchoz, et al.; Immunology 81, 285(1994)/The anti-human CD21 antibody, BU33, identifies equine B cells:S. Mayall, et al.; J. Comp. Pathol. 124, 83 (2001)

MAb to CD22 (human) (RFB4)ANC-171-020 Purified 100µg $ .00ANC-171-030 Biotin 100µg $ .00ANC-171-040 FITC 120 tests $ .00ANC-171-050 R-PE 120 tests $ .00Clone: RFB4. Isotype: Mouse IgG1. Immunogen:

Human tonsil lymphocytes. Specificity: Recognizes

human CD22. Application: FC, IHC (FS, PS), IP.

Lit. Human B cell development. I. Phenotypic differences of Blymphocytes in the bone marrow and peripheral lymphoid tissue: D.Campana, et al.; J. Immunol. 134, 1524 (1985)/The epitope specificityand tissue reactivity of four murine monoclonal anti-CD22 antibodies:J.-L. Li, et al.; Cell Immunol. 118, 85 (1989)

MAb to CD22 (human) (MEM-01)EXB-11-265-C100 100µg $ .00Clone: MEM-01. Isotype: Mouse IgG1. Immuno-

gen: Burkitt’s lymphoma cell line Raji. Specificity:

Recognizes human CD22. Stains only the zone

corresponding to 140kDa. Does not cross-block MAb

to CD22 (human) (RFB4) (Prod. No. ANC-171). Ap-

plication: FC, IP, WB.

MAb to CD72 (human) (3F3)EXB-11-310-C100 100µg $ .00Clone: 3F3. Isotype: Mouse IgG2b. Immunogen:

Normal human lymphocytes from a lymph node.

Specificity: Recognizes human CD72. Application:

FC, IP.

MAb to CD79a (human) (ZL7-4)ANC-235-020 Purified 100µg $ .00ANC-235-030 Biotin 100µg $ .00ANC-235-040 FITC 120 tests $ .00ANC-235-050 R-PE 120 tests $ .00Clone: ZL7-4. Isotype: Mouse IgG1. Immunogen:

Daudi IgM complex. Specificity: Recognizes human

extracellular CD79a. Application: FC, IHC (FS), IP.

Lit. A new antigen identified by the monoclonal antibody UCHB 1 deliversa costimulatory signal to a subset of human B cells: R.J. Armitage, etal.; Eur. J. Immunol. 18, 67 (1988)/Characterization of two monoclonalantibodies (UCL4D12 and UCL3D3) that discriminate between humanmantle zone and marginal zone B cells: J. Smith-Ravin, et al.; Clin.Exp. Immunol. 82, 181 (1990)

MAb to CD79b (human) (SN8/3A2-2E7)ANC-301-020 Purified 100µg $ .00ANC-301-030 Biotin 100µg $ .00ANC-301-040 FITC 120 tests $ .00ANC-301-050 R-PE 120 tests $ .00Clone: SN8/3A2-2E7. Isotype: Mouse IgG1.

Immunogen: Membrane preparation of human B

prolymphocytic leukemia cells. Specificity:

Recognizes the extracellular part of human CD79b.

Detects a band of ~38kDa by Western blot. Appli-

cation: FC, IHC (FS), IP, WB, FUNC (induces signal

transduction in B cells).

Lit. Three new monoclonal antibodies that define a unique antigenassociated with prolymphocytic leukemia/non-Hodgkin’s lymphomaand are effectively internalized after binding to the cell surface antigen:M.Okazaki, et al.; Blood 81, 84 (1993)

MAb to CD100 (human) (133-1C6)ANC-321-020 Purified 100µg $ .00ANC-321-030 Biotin 100µg $ .00ANC-321-040 FITC 120 tests $ .00Clone: 133-1C6. Isotype: Mouse IgM. Immunogen:

PHA stimulated human peripheral blood leukocytes

(PBL). Specificity: Recognizes human CD100. Ap-

plication: FC, IHC (FS), IP.

MAb to IgM (human) (UCHB1)ANC-141-020 Purified 100µg $ .00ANC-141-030 Biotin 100µg $ .00ANC-141-040 FITC 120 tests $ .00ANC-141-050 R-PE 120 tests $ .00Clone: UCHB1. Isotype: Mouse IgG1. Immunogen:

Prolymphocytic leukemic B cells. Specificity:

Recognizes human IgM. Application: FC, IHC (FS), IP.

Lit. A new antigen identified by the monoclonal antibody UCHB 1 deliversa costimulatory signal to a subset of human B cells: R.J. Armitage, etal.; Eur. J. Immunol. 18, 67 (1988)/Characterization of two monoclonalantibodies (UCL4D12 and UCL3D3) that discriminate between humanmantle zone and marginal zone B cells: J. Smith-Ravin, et al.; Clin.Exp. Immunol. 82, 181 (1990)

MAb to IgM (human) (CH2)EXB-11-320-C100 100µg $ .00Clone: CH2. Isotype: Mouse IgG1. Immunogen:

Purified human IgM. Specificity: Recognizes the human

IgM Fc fragment. Application: ELISA, FC, ICC, WB.

B Cell Receptor Signalling

Immunoreceptor Tyrosine-based Activation Motif (ITAM)

CD81

IgMIgLIgL

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Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM)

Lipid Raft

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Lyn

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SHIPSHP1

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CD66a

CD154 [CD40L]

CD40

Phosphatase Kinase

CD40L + Enhancer

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Figure: Stimulation of B cells by rhsCD40L. Dose dependent costimulation

of CD19+ cells by rhsCD40L in the presence of 10ng/ml of IL4 and of

2µg/ml anti-µ antibodies. Note that in the presence of enhancer (Prod.

No. 804-034), the activity of rhsCD40L is increased >1,000 fold.

ReceptorsCD40:Fc (human) (rec.)522-016-C050 50µg $ .00Produced in HEK 293 cells. The cysteine-rich region

(aa 21-193) of human CD40 is fused to the Fc portion

of human IgG1. Specificity: rhCD40:Fc binds human

CD40L (CD154). Application: Inhibits CD40L-

mediated effects. Can be used together with anti-human

IgG1 PAb to detect membrane-bound human CD40L.

Lit. Cysteine 230 is essential for the structure and activity of the cytotoxicligand TRAIL: J.L. Bodmer, et al.; J. Biol. Chem. 275, 20632 (2000)

CD40-muIg Fusion Protein (human)ANC-504-020 Purified 25µg $ .00ANC-504-820 Purified (PF) 25µg $ .00ANC-504-030 Biotin 50 tests $ .00ANC-504-050 R-PE 50 tests $ .00Produced in CHO cells. Soluble molecule consisting of

the extracellular (193 aa) domain of human CD40 fused

to the Fc portion of mouse IgG2a (232 aa). Application:

ELISA, FC, IHC (FS), FUNC (blocks binding of anti-

human CD40 to Raji human tumor cells).

Note: PF = Preservative-free.

Ligands BULKBULKBULKBULKBULKCD40L [CD154], Soluble (human) (rec.)522-015-2010 2x10µg $ .00Produced in E. coli. The extracellular domain of human

CD40L (CD154) (aa 116-261) is fused at the N-

terminus to a linker peptide (6 aa) and a FLAG-tag.

Specificity: rhsCD40L binds to human CD40.

Application: Stimulates growth of B cells. The activity

of rhsCD40L increases 1,000-fold (stimulation in the

ng/ml range) in the presence of a cross-linking enhancer

(see Prod. No. 850-064, below).

Lit. Conversion of membrane-bound Fas(CD95) ligand to its solubleform is associated with downregulation of its proapoptotic activity andloss of liver toxicity: P. Schneider, et al.; J. Exp. Med. 187, 12051 (1998)/CD45 inhibits CD40L-induced microglial activation via negative regulationof the Src/p44/42 MAPK pathway: J. Tan, et al.; J. Biol. Chem. 275, 37224(2000)/Histamine polarizes human dendritic cells into Th2 cell-promotingeffector dendritic cells: G. Caron, et al.; J. Immunol. 167, 3682 (2001)/Synergy between CD40 ligation and IL-4 on fibroblast proliferation involvesIL-4 receptor signaling: S.P. Atamas, et al.; J. Immunol. 168, 1139 (2002)/Suppression of IL-12 Production by Soluble CD40 Ligand: Evidence forInvolvement of the p44/42 Mitogen-Activated Protein Kinase Pathway:M. Wittmann, et al.; J. Immunol. 168, 3793 (2002)

CD40L [CD154], Soluble (human)(rec.) Set850-064-KI01 1 Set $ .00The set contains 1 x 10µg of recombinant human

soluble CD40L (Prod. No. 522-015) plus 2 x 50µg of

an enhancer (Prod. No. 804-034), which increases the

biological activity of rhsCD40L at least 1,000-fold

(see Figure left). Application: Can be used to activate

B cells and dendritic cells.

Lit. Synergy between CD40 ligation and IL-4 on fibroblast proliferationinvolves IL-4 receptor signaling: S.P. Atamas, et al.; J. Immunol. 168, 1139(2002)/The novel IgD binding protein from Moraxella catarrhalis induceshuman B lymphocyte activation and Ig secretion in the presence of Th2cytokines.PG: A. Gjorloff Wingren, et al.; J. Immunol. 168, 5582 (2002)

CD40 & CD40L [CD154]Ligation of B cell CD40 by CD40L (CD154)

expressed on activated T cells is required for

secondary immune responses and germinal centre

formation, stimulating proliferation, differentiation,

isotype switching and upregulation of surface

molecules contributing to antigen presentation.

Selected Review Articles: Immune regulation by CD40-CD40-linteractions - 2; Y2K update: C. van Kooten; Front. Biosci. 5, D880 (2000)/CD40-mediated regulation of immune responses by TRAF-dependentand TRAF-independent signaling mechanisms: A.C. Grammer & P.E.Lipsky; Adv. Immunol. 76, 61 (2000)/The CD40/CD154 receptor/liganddyad: U. Schonbeck & P. Libby; Cell. Mol. Life Sci. 58, 4 (2001)/Signalingby CD40 and its mimics in B cell activation: G.A. Bishop & B.S. Hostager;Immunol. Res. 24, 97 (2001)/CD40-CD40L interaction in Alzheimer’sdisease: J. Tan, et al.; Curr. Opin. Pharmacol. 2, 445 (2002)/Life and deathwithin germinal centres: a double-edged sword: L. Guzman-Rojas, et al.;Immunology 107, 167 (2002)/Life and death within germinal centres: adouble-edged sword: L. Guzman-Rojas, et al.; Immunology 107, 167(2002)/The CD154-CD40 costimulatory pathway in transplantation:Yamada & M.H. Sayegh; Transplantation 73, S36 (2002)/CD40 signalingand autoimmunity: G. Cheng & S.P. Schoenberger; Curr. Dir. Autoimmun.5, 51 (2002)/Prospects for CD40-directed experimental therapy of humancancer: A.W. Tong & M.J. Stone; Cancer Gene Ther. 10, 1 (2003)/Differential regulation of cell survival by CD40: C. Dallman, et al.;Apoptosis 8, 45 (2003)

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CD40L [CD154]-muCD8 FusionProtein (human)ANC-505-020 Purified 25µg $ .00ANC-505-820 Purified (PF) 25µg $ .00ANC-505-030 Biotin 50 tests $ .00ANC-505-040 FITC 50 tests $ .00ANC-505-050 R-PE 50 tests $ .00Produced in CHO cells. Soluble molecule consisting

of the extracellular domain (213 aa) of human

CD40L (CD154) fused to the extracellular (167

aa) domain of mouse CD8α. Specificity: Binds to

CD40 and blocks binding of anti-CD40 MAbs.

Application: ELISA, FC, IHC (FS).

Note: PF = Preservative-free.

Lit. CD40 ligation in B cell activation, isotype switching and memorydevelopment: D. Gray, et al.; Semin. Immunol. 6, 303 (1994)/Hyperexpression of CD40 ligand by B and T cells in human lupus andits role in pathogenic autoantibody production: A. Desai-Mehta, et al.; J.Clin. Invest. 97, 2063 (1996)/A central role of CD40 ligand in the regulationof CD4+ T-cell responses: I.S. Grewal and R.A. Flavell; Immunol.Today 17, 410 (1996)/CD40 and its ligand in host defense: R.J. Noelle;Immunity 4, 415 (1996)/Human native soluble CD40L is a biologicallyactive trimer, processed inside microsomes: F. Pietravalle, et al.; J.Biol. Chem. 271, 5965 (1996)/Functional CD40 ligand is expressed onhuman vascular endothelial cells, smooth muscle cells, andmacrophages: implications for CD40-CD40 ligand signaling inatherosclerosis: F. Mach, et al.; PNAS 94, 1931 (1997)

AntibodiesMAb to CD40 (human) (BE-1)ANC-189-020 Purified 100µg $ .00ANC-189-030 Biotin 100µg $ .00ANC-189-040 FITC 120 tests $ .00ANC-189-050 R-PE 120 tests $ .00Clone: BE-1. Isotype: Mouse IgG1. Immunogen:

Mouse L cell transfectants expressing human

CD40. Specificity: Recognizes human CD40

molecule of about 44kDa. Application: FC, IHC

(FS), IP, FUNC (binding of cross-linked BE-1

partially activates B cells).

Lit. Analysis of expression and function of CD40 on normal and leukemichuman B cell precursors: C.L. Law, et al.; Leukemia 4, 732 (1990)/Assembly and regulation of the CD40 receptor complex in human Bcells: M.R. Kuhne, et al.; J. Exp. Med. 186, 337 (1997)/Characterizationof a CD40-dominant inhibitory receptor mutant: A.M. Mehl, et al.; J.Immunol. 167, 6388 (2001)

MAb to CD40 (human) (EA-5)ANC-300-020 Purified 100µg $ .00ANC-300-030 Biotin 100µg $ .00ANC-300-040 FITC 120 tests $ .00ANC-300-050 R-PE 120 tests $ .00Clone: EA-5. Isotype: Mouse IgG1. Immunogen:

Mouse L cell transfectants expressing human

CD40. Specificity: Recognizes human CD40

molecule of about 44kDa. Application: FC, IHC

(FS), IP, FUNC (binding of cross-linked BE-1

partially activates B cells).

Lit. Analysis of expression and function of CD40 on normal and leukemichuman B cell precursors: C.L. Law, et al.; Leukemia 4, 732 (1990)/Cross-linking CD40 on human B cell precursors inhibits or enhances growthdepending on the stage of development and the IL costimulus: A.W. Larsonand T.W. LeBien; J. Immunol. 153, 584 (1994)/Follicular dendritic cellsinhibit apoptosis in human B lymphocytes by a rapid and irreversibleblockade of preexisting endonuclease: E. Lindhout; J. Exp. Med. 181,1985 (1995)/Assembly and regulation of the CD40 receptor complex inhuman B cells: M.R. Kuhne, et al.; J. Exp. Med. 186, 337 (1997)

CD40-activating MAb - A PotentImmune Response Booster

MAb to CD40 (mouse) (FGK45)805-046-C100 100µg $ 150.00805-046-C500 500µg $ 520.00805-046B-C050 50µg $ .00Clone: FGK45. Isotype: Rat IgG2a. Immunogen:

Recombinant mouse CD40 fusion protein. Specificity:

Recognizes mouse CD40. Application: FC, FUNC

(activates B and NK cells in vivo and in vitro).

Lit. The SCID but not the RAG-2 gene product is required for S mu-Sepsilon heavy chain class switching: A. Rolink, et al.; Immunity 5, 319(1996)/For a comprehensive bibliography please visit our website.

MAb to CD40L [CD154] (Blocking) (24-31)ANC-353-020 Purified 100µg $ .00ANC-353-030 Biotin 100µg $ .00ANC-353-040 FITC 120 tests $ .00ANC-353-050 R-PE 120 tests $ .00Clone: 24-31. Isotype: Mouse IgG1. Immunogen:

Recombinant human CD40L (CD154). Specificity:

Recognizes human and primate CD40L. Detects a

band of ~39kDa by Western blot. This antibody is

widely recognized to be the most specific antibody

for CD40L. Application: FC, IHC (FS), IP, WB, FUNC

(blocks mixed lymphocyte reaction (MLR),

CD40L-induced human B cell proliferation and T

cell dependent B cell differentiation).

Lit. Hyperexpression of CD40 ligand by B and T cells in human lupusand its role in pathogenic autoantibody production: A. Desai-Mehta, etal.; J. Clin. Invest. 97, 2063 (1996)/Human native soluble CD40L is abiologically active trimer, processed inside microsomes: F. Pietravalle,et al.; J. Biol. Chem. 271, 5965 (1996)/Functional CD40 ligand isexpressed on human vascular endothelial cells, smooth muscle cells,and macrophages: implications for CD40-CD40 ligand signaling inatherosclerosis: F. Mach, et al.; PNAS 94, 1931 (1997)/Spleen is aprimary site for activation of platelet-reactive T and B cells in patientswith immune thrombocytopenic purpura: M. Kuwana, et al.; J. Immunol.168, 3675 (2002)

MAb to CD40L [CD154] (human)(Blocking) (MK13A4)805-037-C100 Purified (PF)100µg $ .00805-037B-T100 Biotin 100 tests $ .00805-037F-T100 FITC 100 tests $ .00Clone: MK13A4. Isotype: Mouse IgG1. Immuno-

gen: Recombinant human CD40L (CD154).

Specificity: Recognizes human CD40L. Applica-

tion: FC, FUNC (blocks binding of CD40L to its

receptor CD40).

Note: PF = Preservative-free.

MAb to CD40L [CD154] (mouse) (MR1)804-331-C100 100µg $ .00Clone: MR1. Isotype: Hamster IgG1. Immunogen:

Recombinant mouse CD40L (CD154). Specificity:

Recognizes mouse CD40L. Application: FUNC

(blocks T cell costimulation in vivo, promoting

allograft acceptance and donor-specific tolerance

to secondary skin grafts).

Lit. CD40-gp39 interactions play a critical role during allograft rejection.Suppression of allograft rejection by blockade of the CD40-gp39pathway: C.P. Larsen, et al.; Transplantation 61, 4 (1996)/For acomprehensive bibliography please visit our website.

Hyperacute Rejection Monitor for Transplantations

Monoclonal Antibody to α-Gal Epitope(Galα1→3Galβ1→4GlcNAc-R) (M86)801-090-L002 2ml $ .00801-090-L005 5ml $ .00Clone: M86. Isotype: Mouse IgM. Immunogen:

Rabbit red blood cell membrane. Specificity: Recognizes

synthetic and naturally produced human, mouse, rat,

pig and baboon Galα1-3Gal epitopes on glycoproteins

and glycolipids. Does not cross-react with β-gal

glycoproteins or BSA. Application: ELISA, FC, IHC

(PS), WB, FUNC (can be used for cytotoxicity assays

for α-Gal specific pathways).

Lit. A sensitive assay for measuring alpha-Gal epitope expression oncells by a monoclonal anti-Gal antibody: U. Galili, et al.; Transplantation65, 1129 (1998)/The alpha-gal epitope (Gal alpha 1-3Gal beta 1-4GlcNAc-R) in xenotransplantation: U. Galili; Biochimie 83, 557 (2001) (Review)

ELISA KitsCD40, Soluble (human) ELISA Kit850-262-KI01 1 Kit $ .00Quantity: 96 wells (~80 tests). Sensitivity: 12pg/

ml. Application: For measurement of human CD40

in culture supernatants, human serum, EDTA or

heparinized plasma, amniotic fluid or other body fluids.

CD40L [CD154], Soluble (human)ELISA Kit850-030-KI01 1 Kit $ .00Quantity: 96 wells (~80 tests). Sensitivity: 95pg/

ml. Application: For measurement of human CD40L

(CD154) in culture supernatants or human serum.

CD40 & CD154 [CD40L] continued

B CellSurvival

T CellCostimulation

Plasma CellSurvival?

Ligands BAFF, Soluble (human) (rec.)

522-025-C010 10µg $ 360.00Produced in bacteria. The extracellular domain of human

BAFF (aa 83-285) is fused at the N-terminus to a linker

peptide (6 aa) and a FLAG-tag. Specificity: Binds to

human and mouse (weak) BCMA and TACI.

Application: Stimulates human B cell proliferation.

Lit. For a comprehensive bibliography please visit our website.

BAFF, Soluble (mouse) (rec.)522-052-C010 10µg $ 360.00Produced in HEK 293 cells. The extracellular domain of

mouse BAFF (aa 127-309) is fused at the N-terminus to

a linker peptide (10 aa) and a FLAG-tag. Specificity:

Binds to human (weak) and mouse BCMA and TACI.

Application: Stimulates mouse B cell proliferation.

Continued on Page 4Tomorrow’s Reagents Today™Tomorrow’s Reagents Today™

BAFF, BCMA & the Receptors APRIL,BAFF-R & TACI

Another key player in B cell

biology is BAFF (B-cell

activating factor belonging to

the tumor necrosis factor

family) that is clearly a survival

factor for most B cells. BAFF

is also known as TALL-1

(TNF- and ApoL-related

leukocyte-expressed ligand 1),

BLyS (B lymphocyte stimu-

lator), THANK (a TNF

homolog that activates

apoptosis, nuclear factor-κB

and c-Jun N-terminal kinase),

zTNF4 and TNSF13B. BAFF is produced by

macrophages, monocytes and dendritic cells, and

interferon-γ stimulates the expression of BAFF by

these cells.

APRIL (a proliferation-inducing ligand), also known

as TRDL-1 (TNF-related death ligand-1), is a molecule

related to BAFF and shares some of the BAFF

receptors. APRIL is highly expressed in peripheral

blood lymphocytes, macrophages and monocytes.

BAFF and APRIL both bind to the TNF receptor

superfamily members BCMA (B cell maturation

antigen) and TACI (transmembrane activator and

calcium-modulator and cyclophilin ligand interactor),

but BAFF only binds to BAFF-R. Membrane-bound

and soluble BAFF bind to CD19+ B cells, including

both naive and memory B cells. BAFF is a strong

costimulator of B cells in the presence of B cell receptor

(BCR) crosslinking, promoting the maturation of

splenic T2 B cells. Overexpression of BAFF can

overcome strong death signals that are triggered by

autoantigen binding to the BCR leading to severe

autoimmunity diseases like systemic lupus

erythematosus (SLE), Sjörgen’s syndrome and

rheumatoid arthritis.

Selected Review Articles: APRIL and BAFF connect autoimmunity andcancer: C.F. Ware; J. Exp. Med. 192, F35 (2000)/TNF cytokine family:more BAFF-ling complexities: Y. Laabi, et al.; Curr. Biol. 11, R1013 (2001)/B cells, BAFF/zTNF4, TACI, and systemic lupus erythematosus: T.Dorner & C. Putterman; Arthritis Res. 3, 197 (2001)/The role of TALL-1and APRIL in immune regulation: S.D. Khare & H. Hsu; Trends Immunol.22, 61 (2001)/The role of BAFF in B-cell maturation, T-cell activation andautoimmunity: F. Mackay & C.R. Mackay; Trends Immunol. 23, 113(2002)/BAFFled B cells survive and thrive: roles of BAFF in B-celldevelopment: A.G. Rolink & F. Melchers; Curr. Opin. Immunol. 14, 266(2002)/B cell diversity and longevity in systemic autoimmunity: M. Zouali;Mol. Immunol. 38, 895 (2002)/Systemic lupus erythematosus: a blisslessdisease of too much BLyS (B lymphocyte stimulator) protein: W. Stohl;Curr. Opin. Rheumatol. 14, 522 (2002)//Mechanism of BLyS action in Bcell immunity: R.K. Do & S. Chen-Kiang; Cytokine Growth Factor Rev.13, 19 (2002)/BAFF: a fundamental survival factor for B cells: F. Mackay& J.L. Browning; Nat. Rev. Immunol. 2, 465 (2002)/BAFF: a novel therapeutictarget for autoimmunity: S.L. Kalled; Curr. Opin. Investig. Drugs 3, 1005(2002)/Dendritic cells, BAFF, and APRIL: innate players in adaptiveantibody responses: I. MacLennan & C. Vinuesa; Immunity 17, 235 (2002)/BAFF AND APRIL: A Tutorial on B Cell Survival: F. Mackay, et al.; Annu.Rev. Immunol. 21, 231 (2003)

4

Issue 0301CHF

rhsMegaAPRIL™[APRIL, Soluble (human) (rec.):ACRP30headless(human)]522-035-3010 3x10µg $ 440.00Produced in HEK 293 cells. The extracellular domain of

human APRIL (aa 105-250) is fused to human ACRP30

(aa 16-108). Specificity: Interacts with human BCMA

and TACI. Application: Stimulates proliferation of serum-

starved NIH 3T3 cells.

Lit. APRIL modulates B and T cellimmunity: J.V. Stein, et al.; J. Clin.Invest. 109, 1587 (2002)/DCsinduce CD40-independentimmunoglobulin class switchingthrough BLyS and APRIL: M.B.Litinskiy, et al.; Nat. Immunol. 3,822 (2002)

Receptors BAFF-R:Fc (human) (rec.)

522-060-C050 50µg $ 360.00Produced in HEK 293 cells. The extracellular domain of

human BAFF-R (aa 2-71) is fused to the Fc portion of

human IgG1. Specificity: Binds human and mouse BAFF.

Application: Inhibits rhsBAFF mediated B cell

proliferation.

BCMA:Fc (human) (rec.)522-026-C050 50µg $ 360.00Produced in HEK 293 cells. The extracellular domain

of human BCMA (aa 2-54) is fused to the Fc portion of

human IgG1. Specificity: Binds human and mouse

BAFF and APRIL. Application: Can be used together

with anti-human IgG1 PAb to detect membrane-bound

human and mouse BAFF. Blocks the binding of BAFF

and APRIL to their receptors BCMA and TACI,

inhibiting BAFF- and APRIL-mediated B cell activation.

Lit. BAFF binds to the tumor necrosis factor receptor-like molecule B cellmaturation antigen and is important for maintaining the peripheral B cell population:J.S. Thompson, et al.; J. Exp. Med. 192, 129 (2000) /A soluble form of B cellmaturation antigen, a receptor for the tumor necrosis factor family memberAPRIL, inhibits tumor cell growth: P. Rennert, et al.; J. Exp. Med. 192, 1677(2000) /Maturation of marginal zone and follicular B cells requires B cell activatingfactor of the tumor necrosis factor family and is independent of B cell maturationantigen: P. Schneider, et al.; J. Exp. Med. 194, 1691 (2001)/T cell costimulationby the TNF ligand BAFF: B. Huard, et al.; J. Immunol. 167, 6225 (2001)

TACI:Fc (human) (rec.)522-033-C050 50µg $ 360.00Produced in HEK 293 cells. The extracellular domain

of human TACI (aa 2-118) is fused to the Fc portion of

human IgG1. Specificity: Binds human and mouse

BAFF and APRIL. Application: Blocks the binding of

BAFF and APRIL to their receptors BCMA and TACI,

inhibiting BAFF-mediated B cell activation.

Lit. T cell costimulation by the TNF ligand BAFF: B. Huard, et al.; J.Immunol. 167, 6225 (2001) /Maturation of marginal zone and follicularB cells requires B cell activating factor of the tumor necrosis factorfamily and is independent of B cell maturation antigen: P. Schneider, etal.; J. Exp. Med. 194, 1691 (2001)

TACI:Fc (mouse) (rec.)522-053-C050 50µg $ 360.00Produced in HEK 293 cells. The extracellular

domain of mouse TACI (aa 1-86) is fused to the Fc

portion of human IgG1. Specificity: Binds human

and mouse BAFF and APRIL. Application: Inhibits

rmsBAFF mediated B cell activation.

MAb to APRIL (human) (Aprily-1)804-148-C100 100µg $ 320.00Clone: Aprily-1. Isotype: Mouse IgG1. Immunogen:

Recombinant human APRIL (aa 93-233). Specificity:

Recognizes human APRIL. Does not cross-react with

mouse APRIL. Application: FC, WB (excellent).

MAb to APRIL (human) (Aprily-8)804-149-C100 100µg $ 320.00Clone: Aprily-8. Isotype: Mouse IgG1. Immunogen:

Recombinant human APRIL (aa 93-233). Specificity:

Recognizes human APRIL. Application: FC, ICC

(excellent), WB.

MAb to BAFF (human) (Buffy-1)804-128-C100 100µg $ 360.00804-128F-T100 FITC 100 tests $ 380.00Clone: Buffy-1. Isotype: Rat IgG2a. Immunogen:

rhsBAFF (aa 83-285). Specificity: Recognizes mem-

brane-bound human BAFF. Application: ICC, FC, WB.

Lit. BAFF, a novel ligand of the tumor necrosis factor family, stimulatesB cell growth: P. Schneider, et al.; J. Exp. Med. 189, 1747 (1999)/BAFFbinds to the tumor necrosis factor receptor-like molecule B cellmaturation antigen and is important for maintaining the peripheral B cellpopulation: J.S. Thompson, et al.; J. Exp. Med. 192, 129 (2000)/A solubleform of B cell maturation antigen, a receptor for the tumor necrosisfactor family member APRIL, inhibits tumor cell growth: P. Rennert, etal.; J. Exp. Med. 192, 1677 (2000)

MAb to BAFF (human) (Buffy-XI)804-147-C100 100µg $ 360.00Clone: Buffy-XI. Isotype: Mouse IgG1. Immuno-

gen: Extracellular domain of human BAFF (aa 137-

285). Specificity: Recognizes C-terminal but not the

stalk of human BAFF. Application: WB.

PAb to BAFF (CT)210-799-C100 100µg $ 240.00From rabbit. Immunogen: Synthetic peptide corre-

sponding to C-terminal aa 254-269 of human BAFF.

Specificity: Recognizes human, mouse and rat BAFF.

Application: WB.

MAb to BCMA (human) (Vicky-1)804-151-C100 100µg $ 360.00Clone: Vicky-1. Isotype: Rat IgG1. Immunogen:

Recombinant human BCMA (aa 2-54). Specificity:

Recognizes human BCMA. Application: FC, ICC.

MAb to TACI (human) (1A1)804-153-038-C050 50µg $ 350.00Clone: 1A1. Isotype: Rat IgG2a. Immunogen:

Rat RBL expressing human TACI. Specificity:

Recognizes human TACI. Application: FC, IHC

(PS), FUNC.

PAb to TACI (human)210-800-C100 Purified 100µg $ 310.00From rabbit. Immunogen: Synthetic peptide corre-

sponding to aa 116-132 of human TACI. Specificity:

Recognizes human TACI. Application: WB.

Antibodies MAb to APRIL (Sacha-1)

804-141-C100 100µg $ 290.00Clone: Sacha-1. Isotype: Rat IgG2a. Immunogen:

Recombinant human APRIL (aa 105-250) fused to

human ACRP30headless (aa 16-108). Specificity:

Recognizes human and mouse APRIL. Application:

FC (excellent), ICC.

MAb to BAFF (human) (Buffy-2)804-131-C100 100µg $ 360.00804-131F-T100 FITC 100 tests $ 380.00Clone: Buffy-2. Isotype: Rat IgM. Immunogen:

rhsBAFF (aa 83-285). Specificity: Recognizes mem-

brane-bound human and mouse (weak) BAFF. Appli-

cation: IHC (FS, PS), WB.

Lit. Association of BAFF/BLyS overexpression and altered B celldifferentiation with Sjogren’s syndrome: J. Groom, et al.; J. Clin. Invest.109, 59 (2002)

BAFF, BCMA & the Receptors APRIL, BAFF-R & TACI continued

Serum 0.2% Serum 0.2% + rhs APRIL™Mega

1

0.8

0.6

0.4

0.2

0

OD

(49

0n

m)

Figure: rhsMegaAPRIL™ induces Swiss NIH-3T3 cells to proliferate in

low serum conditions.

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

0 1 10 100

ng/ml

Rati

o%

livin

g/%

dead

cell

s

Figure: rhBAFF-R:Fc inhibits

rhsBAFF-mediated activation of

freshly isolated splenocytes.

FL2-H

Co

un

ts

01

02

03

04

05

06

07

08

0

10 10 10 10 100 1 2 3 4

Figure: Sacha-1 anti-APRIL detects

membrane-bound human APRIL by

FACS.

Moc

khA

PR

ILhB

AFF

175

8362

47

32

25

16f

Figure: Western blot of total cell extracts from HEK 293 cells

transfected with the indicated expression vector. Aprily-1 reacts

specifically with hAPRIL.

hu-APRIL MockA

pri

ly-8

Figure: Immunostaining of HEK 293 T cells transfected with a human

APRIL expression plasmid (left panel), or mock transfected (right panel)

by Aprily-8.

Figure: Membrane-bound human

BAFF detected by Clone Buffy-1.

Left panel: ICC; right panel: phase

contrast. Lower panel: 293-wt

control.

Figure: Flow cytometric profile of HEK 293 cells stably transfected with

a BAFF-expression plasmid (1). Control (2) are Mock transfected HEK

293 cells. Optimal concentration range is 0.5-5µg/ml.

Figure: Staining of paraffin section of

synovial tissue from a patient with

Rheumatoid Arthritis. Arrows indicate

vessels (20x) staining positive for BAFF

using Buffy-2.

hAP

RIL

hBA

FFm

BA

FF

175

83

62

47

32

25

16f

Figure: Western blot of total cell extracts from HEK 293 cells

transfected with the indicated expression vector.

Full length BCMA

Acetone

Mock

Formaldehyde

Figure: Immunostaining of HEK 293 cells transfected with a human

BCMA expression plasmid (left panels), or mock transfected (right panel).

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