Commensal Microbe-specific Activation of B2 Cell Subsets Contributes to Atherosclerosis Development Independently of Lipid Metabolism.
The relation between B2 cells and commensal microbes during atherosclerosis remains largely unexplored. Here we show that under hyperlipidemic conditions intestinal microbiota resulted in recruitment and ectopic activation of B2 cells in perivascular adipose tissue, followed by an increase in circulating IgG, promoting disease development. In contrast, disruption of the intestinal microbiota by a broad-spectrum antibiotic cocktail (AVNM) led to the attenuation of atherosclerosis by suppressing B2 cells, despite the persistence of serum lipid abnormalities. Furthermore, pharmacological depletion of B2 cells with an anti-B2-cell surface CD23 antibody also attenuated commensal microbe-induced atherosclerosis. Moreover, expression analysis of TLR-signaling-related genes in the activated B2 cell subsets, assessed using the Toll-Like Receptor Signaling Pathway RT2 Profiler PCR Array, confirmed activation of the B2-cell autoantibody-production axis, which was associated with an increased capacity of B2 cells to bind to intestinal microbiota. Together, our findings reveal the critical role of commensal microbe-specific activation of B2 cells in the development of atherogenesis through lipid metabolism-independent mechanisms.
['Chen|Lin|L|', 'Ishigami|Tomoaki|T|', 'Nakashima-Sasaki|Rie|R|', 'Kino|Tabito|T|', 'Doi|Hiroshi|H|', 'Minegishi|Shintaro|S|', 'Umemura|Satoshi|S|']
D000818:Animals D000900:Anti-Bacterial Agents D050197:Atherosclerosis D016175:B-Lymphocyte Subsets D016000:Cluster Analysis D016207:Cytokines D004195:Disease Models, Animal D000069196:Gastrointestinal Microbiome D015870:Gene Expression D020869:Gene Expression Profiling D018836:Inflammation Mediators D050356:Lipid Metabolism D008213:Lymphocyte Activation D008297:Male D051379:Mice D018345:Mice, Knockout D008954:Models, Biological D058226:Plaque, Atherosclerotic D015398:Signal Transduction D051193:Toll-Like Receptors D055114:X-Ray Microtomography
B2 cell Atherosclerosis Intestinal microbiota Inflammation TLR signaling