The role of CD45 in the regulation of B cell subset functions in Atherosclerosis

Abstract

Atherosclerosis is an inflammatory disease of the large and medium size arteries characterized by deposition of oxidized lipids within the vessel. While specific self-antigens are not well characterized, data show that the immune response is involved in atherogenesis. The role of B cells in atherosclerosis is subset specific. FO B cells are proatherogenic, while B1 and MZ B cells serve as protective. B cell receptor signaling is important in B cell activation, differentiation, and functions, while important costimulatory molecules, like CD45, assist in initiating signal propagation. To date, it is unknown whether B cell subsets respond differently to BCR signaling or if CD45-dependent regulation of BCR signaling is subset specific in homeostatic or atherosclerotic conditions. Taking advantage of transgenic mice that express low levels of CD45(CD45L/L), we examined activation of CD45L/L B cells through Ca2+ flux. We show that BCR-induced B cell activation differs between subsets and CD45-dependent modulation of BCR signaling is subset specific. MZ and B1 have high levels of Ca2+ flux, with MZ B cell activation the most affected by CD45 expression. To test the effects of CD45L/L B in atherosclerosis, we performed adoptive transfer of CD45L/L or WT B cells into B cell-deficient atherosclerotic prone mice. After 23–38 wks of western diet feeding, CD45L/L B cell recipients had increased lesion formation despite an increase of protective MZ B cells. This increase in atherogenesis could be due to MZ CD45L/L B cells having reduced activation, disrupting their protective ability. This suggests that the subset-specific modulation of BCR signaling through CD45 plays a role in the regulation of B cell functions in atherosclerosis. This work was supported by American Heart Association AIREA grant 8AIREA33960546.