Immune opsonins modulate BLyS/BAFF release in a receptor-specific fashion.
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 Fcgamma receptor cross-linking triggers a rapid release of soluble, biologically active BLyS/BAFF from myeloid cells. Surprisingly, this function is primarily mediated by FcgammaRI, but not FcgammaRIIa 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 Fcgamma receptor, which can also enhance Ag uptake and presentation, provides a unique opportunity to facilitate Ab production. These results provide a mechanism by which Fcgamma receptors can elevate circulating BLyS levels and promote autoantibody production in immune complex-mediated autoimmune diseases.
Li
Xinrui
X
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Su
Kaihong
K
Ji
Chuanyi
C
Szalai
Alexander J
AJ
Wu
Jianming
J
Zhang
Yan
Y
Zhou
Tong
T
Kimberly
Robert P
RP
Edberg
Jeffrey C
JC
D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009895:Opsonin Proteins / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*
D053264:B-Cell Activating Factor; C489017:FCGR1A protein, human; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D017452:Receptors, IgG; C505719:TNFSF13B protein, human; D002097:C-Reactive Protein