174 Total antibody deficiency in B cell sufficient mice enhances atherosclerosis

Background and aim Extensive studies have revealed an important protective function for IgM antibodies from B1a cells in atherosclerosis, whereas the role of B2 cells and IgG antibodies is uncertain, with both pro- and anti-atherogenic actions reported. The aim of this study was to specifically target antibodies but not other B cell functions and determine the effect on mouse atherosclerosis. Methods We created MB1-Cre x XBP1 fl/fl mice that have B cell specific deficiency in the unfolded protein response transcription factor XBP1, previously reported to result in a specific antibody secretion defect. Specific antibody responses were assessed by ELISA and ELISpot after immunisation with NP-chicken gamma globulin. Chimeric Ldlr -/– mice with bone marrow from MB1-Cre x XBP1 fl/fl or control mice were fed a western diet for 8 weeks. Results B cell XBP1 deficiency led to significantly attenuated antibody secretion after NP-CGG immunisation. Analysis of ldlr –/– chimeric mice revealed enhanced atherosclerosis progression in MB1-Cre x XBP1 fl/fl recipients. These mice displayed severely attenuated serum IgM, IgG and IgE levels, but intact spleen, lymph node and peritoneal B cells. There were no differences in total cholesterol levels. Antibody deficiency was associated with enhanced pro-atherogenic Th1 CD4 + T cell immunity. Conclusions Antibodies have an overall protective effect on atherosclerosis and B2 cell antibodies are not responsible for enhanced atherosclerosis in IgM-deficient mice. Other B cell functions may be pathogenic in atherosclerosis.