| First Author | Bagchi-Chakraborty J | Year | 2019 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 39 |
| Issue | 7 | Pages | 1379-1389 |
| PubMed ID | 31092015 | Mgi Jnum | J:306796 |
| Mgi Id | MGI:6709639 | Doi | 10.1161/ATVBAHA.118.312272 |
| Citation | Bagchi-Chakraborty J, et al. (2019) B Cell Fcgamma Receptor IIb Modulates Atherosclerosis in Male and Female Mice by Controlling Adaptive Germinal Center and Innate B-1-Cell Responses. Arterioscler Thromb Vasc Biol 39(7):1379-1389 |
| abstractText | Objective- Investigate the impact of modulating B cell FcgammaRIIb (Fcgamma receptor IIb) expression on atherosclerosis. Approach and Results- Western diet-induced atherosclerosis was assessed in Ldlr(-)(/-) or Apoe(-/-) mice with B cell-specific overexpression of FcgammaRIIb or with an FcgammaRIIb promoter mutation that alters FcgammaRIIb expression in germinal center (GC) B cells. In males, overexpression of FcgammaRIIb on B cells severely reduced activated, class switched B cell responses, as indicated by reductions in GC B cells, plasma cells, and serum IgG but not IgM antibodies. Male mice overexpressing FcgammaRIIb developed less atherosclerosis, suggesting a pathogenic role for GC B cell IgG responses. In support of this hypothesis, male mice with a promoter polymorphism-driven reduction in FcgammaRIIb on GC B cells but not plasma cells have a converse phenotype of enhanced GC responses and IgG2c antibodies and enhanced atherosclerosis. IgG2c significantly enhanced TNF (tumor necrosis factor) secretion by CD11b(+) CD11c(+) cells expressing the high-affinity receptor FcgammaRIV. In females, overexpression of FcgammaRIIb on B cells not only reduced GC B cell responses but also substantially reduced B-1 cells and IgM antibodies, which translated into acceleration of atherosclerosis. Promoter-driven reduction in FcgammaRIIb did not alter GC B cell responses in females and, therefore, had no impact on atherosclerosis. Conclusions- B cell FcgammaRIIb differentially alters proatherogenic adaptive GC B cell and atheroprotective innate B-1 responses in male and female mice fed a western diet. Our results highlight the importance of a better understanding and ability to selectively target B cell responses in future immunotherapeutic approaches against human cardiovascular disease. Visual Overview- An online visual overview is available for this article. |
