TY - JOUR
T1 - Immune opsonins modulate BLyS/BAFF release in a receptor-specific fashion
AU - Li, Xinrui
AU - Su, Kaihong
AU - Ji, Chuanyi
AU - Szalai, Alexander J.
AU - Wu, Jianming
AU - Zhang, Yan
AU - Zhou, Tong
AU - Kimberly, Robert P.
AU - Edberg, Jeffrey C.
PY - 2008/7/15
Y1 - 2008/7/15
N2 - 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 Fcγ receptor cross-linking triggers a rapid release of soluble, biologically active BLyS/BAFF from myeloid cells. Surprisingly, this function is primarily mediated by FcγRI, but not FcγRIIa 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 Fcγ receptor, which can also enhance Ag uptake and presentation, provides a unique opportunity to facilitate Ab production. These results provide a mechanism by which Fcγ receptors can elevate circulating BLyS levels and promote autoantibody production in immune complex-mediated autoimmune diseases.
AB - 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 Fcγ receptor cross-linking triggers a rapid release of soluble, biologically active BLyS/BAFF from myeloid cells. Surprisingly, this function is primarily mediated by FcγRI, but not FcγRIIa 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 Fcγ receptor, which can also enhance Ag uptake and presentation, provides a unique opportunity to facilitate Ab production. These results provide a mechanism by which Fcγ receptors can elevate circulating BLyS levels and promote autoantibody production in immune complex-mediated autoimmune diseases.
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U2 - 10.4049/jimmunol.181.2.1012
DO - 10.4049/jimmunol.181.2.1012
M3 - Article
C2 - 18606652
AN - SCOPUS:49049115395
SN - 0022-1767
VL - 181
SP - 1012
EP - 1018
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -