Background: The CD32 (FcγII) receptor is involved in the regulation of the B cell response to antigen. The sole Fc receptor demonstrated in mice is the inhibitory FcγIIB receptor. Crosslinking this receptor does not lead to downstream signaling or cell activation. Instead, when immune complexes bind to Fcy on murine B cells, cell activation through the B cell antigen receptor is attenuated. The objective of this study was to evaluate the expression of the FcγII receptor and the response to immune complex stimulation in human B cells. Methods: Human lymphoblastoid, peripheral and tonsillar B cells were stained with anti-CD32 antibodies IV.3 and 8.26 to determine the relative expression of the activating (FcγIIA) and inhibitory (FcγIIB) isoforms of CD32. Tetanus immune complexes were added to B cells and the activation of c-Jun amino-terminal kinase was assayed. Results: Unlike murine cells, human B cells express high levels of the activating form of the Fcγ receptor IIA. Addition of immune complexes to peripheral B cells resulted in signaling of Jun kinase, an important downstream kinase involved in the regulation of B cell function. The level of expression of FcγIIA on human B cells was not uniform, but depended on activation status. Peripheral blood B cells expressed high levels of FcγIIA, while tonsillar B cells predominantly expressed FcγIIB. Furthermore, when peripheral B cells were activated, the expression of FcγIIA relative to FcγIIB decreased. Conclusion: The response of human B cells to binding of immune complexes depends on the relative expression of activating (FcγIIA) versus inhibitory (FcγIIB) receptors.

Sidman CL, Unanue ER: Control of B lymphocyte function: Inactivation of mitogenesis by interactions with surface immunoglobulin and Fc-receptor molecules. J Exp Med 1976;144:882–896.
Muta T, Kurosaki T, Misulovin Z, Sanchez M, Ravetch JV: A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B cell receptor signaling. Nature 1994;368:70–73.
D’Ambrosio D, Hippen KL, Minskoff SA, Mellman I, Pani G, Siminovitch KA, Cambier JC: Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by FcγRIIB1. Science 1995;268:293–297.
Ashman RF, Peckham D, Stunz LL: Fc receptor off-signal in the B cell involves apoptosis. J Immunol 1996;157:5–11.
Daeron M, Latour S, Malbeck O, Espinosa E, Pinna P, Pasmans S, Fridman WH: The same tyrosine-based inhibition motif in the intracytoplasmic domain of FcγRIIB regulates negatively BCR-, TCR- and FCR-dependant cell activation. Immunity 1995;3:635–646.
Koncz G, Gergely J, Sarmay G: FcγRIIB inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in FcγR-transfected human B cells. Int Immunol 1998;10:141–146.
Brooks DG, Qui WQ, Luster AD, Ravetch JV: Structure and expression of human IgG FcRII (CDw32): Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med 1989;170:1369–1385.
Budde P, Bewarder N, Weinrich V, Frey J: Biological functions of human FcγRIIa/FcγRIIc in B cells. Eur J Cell Biol 1994;64:45–60.
Budde P, Bewarder N, Weinrich V, Schulzeck O, Frey J: Tyrosine-containing sequence motifs of the human immunoglobulin G receptors FcRIIB1 and FcRIIB2 are essential for endocytosis and regulation of calcium flux in B cells. J Biol Chem 1994;269:30636–30643.
Van Den Herik-Oudik IE, Westerdaal NAC, Henriquez NV, Capel PJA, Van Der Winkel JGV: Functional analysis of human FcγRII (CD32) isoforms expressed in B lymphocytes. J Immunol 1994;152:574–585.
Budde P, Weinrich V, Sondermann P, Bewarder N, Kilian A, Schulzek O: Specificity of CD32 mAb for FcγIIA, FcγIIB1 and FcγIIB2 expressed in transfected mouse B cells and BHK-21 cells; in Schlossman A (ed): Leukocyte Typing V: White Cell Differentiation Antigens. Oxford, Oxford University Press, 1995, vol 1, pp 823–826.
Hulett MD, Hogarth PM: Molecular basis of Fc receptor function. Adv Immunol 1994;57:1–127.
Sakata N, Patel HR, Terada N, Aruffo A, Johnson GL, Gelfand EW: Selective activation of c-Jun kinase mitogen-activated protein kinase by CD40 on human B-cells. J Biol Chem 1995;270:30823–30828.
Hazan-Halevy I, Seger R, Levy R: The requirement of both extracellular regulated kinase and p38 mitogen-activated protein kinase for stimulation of cytosolic phospholipase A2 activity by either Fcgamma RIIA or Fcgamma RIIIB in human neutrophils. A possible role for pyk2 but not for the Grb2-Sos-Shc complex. J Biol Chem 2000;275:12416–12423.
Splawski JB, Lipsky PE, Eisenstein EM, Chua KS: Isolation of B cell populations; in Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM, Strober W (eds): Current Protocols in Immunology Online. New York, John Wiley and Sons, 2003, Unit 7.5, last retrieved January 15, 2004 from
Kepley CL, Cambier JC, Morel PA, Lujan D, Ortega E, Wilson BS, Oliver JM: Negative regulation of FcγRI signaling by FcγRII costimulation in human blood basophils. J Allergy Clin Immunol 2000;106:337–348.
Uckun F, Schieven G, Dibirdik I, Chandan-Langlie M, Tuel-Ahlgren L, Ledbetter JA: Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover, and multiple previously unidentified serine/threonine-specific protein kinases by the pan-B cell receptor CD40/Bp50 at discrete developmental stages of human B cell ontogeny. J Biol Chem 1991;266:17478–17485.
Fridman WH, Bonnerot C, Daeron M, Amigorena S, Teillaud JL, Sautes S: Structural basis of Fcγ receptor functions. Immunol Rev 1992;125:49–76.
Metes D, Ernst LK, Chambers WH, Sulica A, Haberman RB, Morel PA: Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcγRIIC gene. Blood 1998;91:72369–2380.
Haimovich B, Regan C, DiFazio L, Ginalis E, Purohir U, Rowley RB, Bolen J, Grego R: The FcγRII receptor triggers pp123FAK phosphorylation in platelets. J Biol Chem 1996;271:16332–16337.
Liang L, Huang CK: Tyrosine phosphorylation induced by cross-linking of Fcγ receptor type II in human neutrophils. Biochem J 1995;306:489–495.
Sarmay G, Roznyay Z, Konz G, Danilkovich H, Gegely J: The alternative splicing of human FcγRII mRNA is regulated by activation of B cells with mIGM cross-linking, interleukin-4 or phorbol ester. Eur J Immunol 1995;25:262–268.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.