Investigating The Role Of B Cell Signaling In Atherosclerosis

Abstract INTRODUCTION Atherosclerosis is an inflammatory disease of the large and medium size arteries. While specific antigens are not well characterized, strong data demonstrate that the immune response is involved in atherogenesis. The role of B cells in atherosclerosis is B cell specific: B2 cells are proatherogenic and B1 and MZ B cells serve as protective. B cell activation is dependent on B cell receptor signaling along with a secondary signal, such as CD45. To date, it is unknown how CD45 signaling regulates activation and functions of B cells in atherosclerosis. METHODS We took advantage of a previously characterized transgenic mice that express low levels of CD45 (CD45L/L). We performed adoptive transfer of CD45L/L or WT B cells into B cell-deficient mice injected with AAV-PSCK-9 to induce atherosclerosis. After 16 wks of a western diet feeding aortas were collected and stained with Oil Red O. Spleens from the CD45L/L and WT recipients were analyzed by FACS and isolated splenic B cells were tested in BCR-induced Ca2+ flux, proliferation, and survival assays. RESULTS and CONCLUSIONS Our preliminary data demonstrate that low CD45 expression by B cells increases atherosclerosis in the CD45L/L vs WT recipients. Unexpectedly, elevated aortic plaque burden was accompanied by decrease in pathological Tfh cells and a significant elevation in protective B1 B cells in the CD45L/L compared to WT recipients. Future analysis will determine levels of proliferation and activation of B cells in both groups. These results suggest that CD45-dependent activation of B cells impacts the distribution of B cell subsets and highlight a potential role of BCR-related signaling in the regulation of immunity in atherosclerosis.