Antibodies binding oxidised epitopes on apoptotic cells and oxidised forms of LDL form an important protective barrier slowing the development of atherosclerosis. However, not all B cell functions or subsets are protective since adaptive B2 cell depletion is atheroprotective and autoimmunity is associated with accelerated atherosclerosis. The inhibitory IgG receptor FcÎ³RIIb is the only IgG receptor found on B cells and also counteracts pro-inflammatory signalling from activating FcÎ³ receptors in macrophages and dendritic cells. Studies on FcÎ³RIIb knockout mice demonstrate significant regulation of atherosclerosis but contrasting effects depending on the genetic background, suggesting the need for alternative approaches. We have analysed the effects of B cell-specific over-expression of FcÎ³RIIb using a previously characterised transgenic mouse strain. FcÎ³RIIb over-expression was confirmed to be specific for B cells and was equal between genders. There was only minor impacts on mature B cell levels, but FcÎ³RIIb over-expression significantly attenuated plasma cell levels and serum antibody titres. Female, but not male, FcÎ³RIIb-B cell transgenic mice on the ApoE-/- background develop significantly enhanced atherosclerosis after 6 weeks high fat diet compared to non-transgenic littermates. Females but not males had significantly decreased oxidised epitope-specific IgM levels and B1a cells in spleen and peritoneal lavage. In vitro, B1 cells from female ApoE-/- mice were more susceptible to FcÎ³RIIb-induced apoptosis. Overall, our study highlights a potential difference in B1 cell biology between males and females, and supports the investigation of gender specific effects of autoimmune-linked FcÎ³RIIb polymorphisms on human cardiovascular disease.
- B Cells
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