Anti-FCGR2B monoclonal antibody, clone DDH47 [FITC]

The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the promoter region is suggested to be one most plausible susceptibility gene for systemic lupus erythematosus (SLE). We previously found that there is a strong epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE observed in BXSB males neither develops in BXSB females nor in the congenic BXSB.IIBB6 males carrying wild C57BL/6-type Fcgr2b. Present studies examined whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated SLE susceptibility genes. Comparison of disease features between SLE-prone (NZW x BXSB) F1 females and the congenic (NZW x BXSB.IIBB6) F1 females carrying wild-type Fcgr2b showed that, as compared with findings in the former, SLE features including activation/proliferation of not only B cells but also T cells and monocytes/macrophages were all inhibited in the latter. It was concluded that the autoimmune-type Fcgr2b promotes and the wild-type inhibits SLE through mechanisms that promote and suppress activation/proliferation of a wide variety of immune cells, respectively. Thus, the Fcgr2b polymorphism is a key genetic element for not only Yaa-related but also Yaa-unrelated lupus. (C) 2009 Elsevier Ltd. All rights reserved.

Immune complex (IC)-mediated tissue inflammation is controlled by stimulatory and inhibitory IgG Fc receptors (Fc gamma Rs). Systemic lupus erythematosus is a prototype of IC-mediated autoimmune disease; thus, imbalance of these two types of Fc gamma Rs is probably involved in pathogenesis. However, how and to what extent each Fc gamma R contributes to the disease remains unclear. In lupus-prone BXSB mice, while stimulatory Fc gamma Rs are intact, inhibitory Fc gamma RIIB expression is impaired because of promoter region polymorphism. To dissect roles of stimulatory and inhibitory Fc gamma Rs, we established two gene-manipulated BXSB strains: one deficient in stimulatory Fc gamma Rs (BXSB.,gamma(-/-)) and the other carrying wild-type Fcgr2b (BXSB.IIBB6/(B6)). The disease features were markedly suppressed in both mutant strains. Despite intact renal function, however, BXSB.,gamma(-/-) had IC deposition in glomeruli associated with high-serum IgG anti-DNA Ab levels, in contrast to BXSB.IIB, which showed intact renal pathology and anti-DNA levels. Lymphocytes in BXSB.,gamma(-/-) were activated, as in wild-type BXS% but not in BXSB.IIBB6/B6. Our results strongly suggest that both types of Fc gamma Rs in BXSB mice are differently involved in the process of disease progression, in which, while stimulatory Fc gamma Rs play roles in effecter phase of IC-mediated tissue inflammation, the BXSB-type impaired Fc gamma RIIB promotes spontaneous activation of self-reactive lymphocytes and associated production of large amounts of autoantibodies and ICs.