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FcRIIB Regulates Autoreactive Primary Antibody-Forming Cell, but Not Germinal Center B Cell, Activity¹

Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107

The low-affinity FcR for IgG FcRIIB suppresses the development of IgG autoantibodies and autoimmune disease in normal individuals, but how this effect is mediated is incompletely understood. To investigate this issue, we created FcRIIB-deficient versions of two previously described targeted BCR-transgenic lines of mice that contain follicular B cells with specificity for the hapten arsonate, but with different levels of antinuclear autoantigen reactivity. The primary development and tolerance of both types of B cells were unaltered by the absence of FcRIIB. Moreover, the reduced p-azophenylarsonate-driven germinal center and memory responses characteristic of the highly autoreactive clonotype were not reversed by an intrinsic FcRIIB deficiency. In contrast, the p-azophenylarsonate-driven primary Ab-forming cell responses of both clonotypes were equivalently increased by such a deficiency. In total, our data do not support the idea that FcRIIB directly participates in the action of primary or germinal center tolerance checkpoints. In contrast, this receptor apparently contributes to the prevention of autoimmunity by suppressing the production of autoreactive IgGs from B cells that have breached tolerance checkpoints and entered the Ab-forming cell pathway due to spontaneous, or cross-reactive, Ag-mediated activation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant RO1 AI 46806 (to T.M.).

² Address correspondence and reprint requests to Dr. Ziaur S. M. Rahman, Department of Microbiology and Immunology and Kimmel Cancer Center, Jefferson Medical College, Bluemle Life Sciences Building 708, 233 South 10th Street, Philadelphia, PA 19107-5541. E-mail address: zrahman{at}mail.jci.tju.edu

³ Abbreviations used in this paper: IC, immune complex; TD, T cell dependent; AFC, Ab-forming cell; GC, germinal center; FO, follicular; FDC, FO dendritic cell; KLH, keyhole limpet hemocyanin; Ars, p-azophenylarsonate; PNA, peanut lectin (agglutinin); MZ, marginal zone; ANA, antinuclear autoantibody; RQ, relative quantification; MOMA-1, metallophillic macrophage-1; Blimp-1, B lymphocyte-induced maturation protein-1.

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