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206 B Cell-Specific FC Gamma Receptor IIB Over-Expression Enhances Atherosclerosis by Inhibiting B1 Cells
  1. Andrew Sage,
  2. Deirdre Murphy,
  3. Leanne Masters,
  4. Lauren Kitt,
  5. Reem Assil,
  6. Ziad Mallat
  1. University of Cambridge


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 FcγRIIb is the only IgG receptor found on B cells and also counteracts pro-inflammatory signalling from activating Fcγ receptors in macrophages and dendritic cells. Studies on FcγRIIb 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 FcγRIIb using a previously characterised transgenic mouse strain. FcγRIIb 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 FcγRIIb over-expression significantly attenuated plasma cell levels and serum antibody titres. Female, but not male, FcγRIIb-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 FcγRIIb-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 FcγRIIb polymorphisms on human cardiovascular disease.

  • B Cells
  • IgM
  • Atherosclerosis

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