title: Immune opsonins modulate BLyS/BAFF release in a receptor-specific fashion.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Li
authors.forename: Kaihong
authors.initials: K
authors.lastname: Su
authors.forename: Chuanyi
authors.initials: C
authors.lastname: Ji
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai
authors.forename: Jianming
authors.initials: J
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
mesh_terms: 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*
chemical_list: 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