-
Views
-
Cite
Cite
Tayab Waseem, William Coles Keeter, Alina Moriarty, Stefan Edemobi, Michael Pham, Andrew Getahun, John C Cambier, Elena Galkina, B cell anergy: Atheroprotective, yet vulnerable to atherosclerotic conditions, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 121.14, https://doi.org/10.4049/jimmunol.202.Supp.121.14
- Share Icon Share
Abstract
Anergy is the major mechanism for peripheral tolerance. Recent reports highlight the role of B cell anergy in lupus, type 1 diabetes, and arthritis, but little is known about the induction and maintenance of anergic B cells within atherosclerosis. ARS/A1 mice have B cells that respond with moderate affinity to Ars hapten, but also cross-react with low affinity to endogenous ssDNA resulting in an anergic B cell repertoire. To explore the role of B cell anergy in atherosclerosis, we examine ARS/A1 and BL/6 littermate controls that have been fed a western diet for 16 weeks and injected with AAV-PCSK9 to induce atherosclerosis. Our data showed that ARS/A1 mice had 44% less lesions, and a decreased inflammatory profile compared to BL/6 controls. The role of B cells in atherosclerosis varies by B cell subsets. Whereas marginal zone B cells (MZ) are atheroprotective, follicular B cells (FO) accelerate atherosclerosis. To further explore how an atherosclerotic environment affects B cell subsets, we compared the percentages of splenic B cell subtypes in PCSK9-treated vs healthy ARS/A1 controls. Our data showed a significant decrease in ARS/A1 FO B cells and an increase in ARS/A1 MZ B cells suggesting a skewing of B cell subsets upon exposure to atherosclerotic conditions in ARS/A1 mice. Surprisingly, we detected an increased calcium response upon BCR crosslinking and increase levels of CD86 in B cells from PCSKS-9-injected ARS/A1 vs BL/6 controls. Overall, our data suggests that while anergy is atheroprotective, the inflammatory environment seen within atherosclerosis may prime B cells to increase the responsiveness of anergic B cells to activation.