The role of CD45 in the regulation of B cell subset functions in Atherosclerosis
JOURNAL OF IMMUNOLOGY(2022)
摘要
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.
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关键词
atherosclerosis,cd45
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