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Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-Specific Fashion¹

Xinrui Li^*,, Kaihong Su^*, Chuanyi Ji^*, Alexander J. Szalai^*, Jianming Wu^*, Yan Zhang^*, Tong Zhou^*, Robert P. Kimberly^*,, and Jeffrey C. Edberg^2,*,

^* Division of Clinical Immunology and Rheumatology, Department of Medicine, Cell Biology, and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294

TNF ligand superfamily member 13B (B lymphocyte stimulator (BLyS), B cell activating factor (BAFF)) promotes primary B cell proliferation and Ig production. While the soluble form of BLyS/BAFF is thought to be the primary biologically active form, little is known about the regulation of its cleavage and processing. We provide evidence that Fc receptor cross-linking triggers a rapid release of soluble, biologically active BLyS/BAFF from myeloid cells. Surprisingly, this function is primarily mediated by FcRI, but not FcRIIa as defined by specific mAb, and can be initiated by both IgG and C reactive protein as ligands. The generation of a B cell proliferation and survival factor by both innate and adaptive immune opsonins through engagement of an Fc receptor, which can also enhance Ag uptake and presentation, provides a unique opportunity to facilitate Ab production. These results provide a mechanism by which Fc receptors can elevate circulating BLyS levels and promote autoantibody production in immune complex-mediated autoimmune diseases.

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 grants from the National Institutes of Health (AR42476, AR33062, P01-AR49084, and M01-RR00032).

² Address correspondence and reprint requests to Dr. Jeffrey C. Edberg, University of Alabama at Birmingham, 1825 University Boulevard, Room 207 Shelby, Birmingham, AL 35294. E-mail address: jedberg{at}uab.edu

³ Abbreviations used in this paper: BLyS, B lymphocyte stimulator; BAFF, B cell activating factor; CRP, C reactive protein; GM, goat anti-mouse IgG; MNC, mononuclear cell.