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- W4313356104 abstract "Abstract Existing evidence demonstrates that B1 cells exert protective effects in atherosclerosis through production of anti-inflammatory natural IgM antibodies that recognize oxidation-specific epitopes (OSE), such as MDA-LDL, present in diseased arteries. The bone marrow is a known niche for B1 antibody production. However, the mechanisms underlying B1 localization to the bone marrow and B1 antibody production are currently unclear. Our lab has correlated surface marker expression on peripheral blood mononuclear cells with clinical markers of atherosclerosis in a human cohort. Expression of the chemokine receptor CXCR4 on circulating B1 cells associates with decreased plaque burden in coronary arteries and increased plasma levels of anti-MDA-LDL IgM antibodies. To study the role of CXCR4 in modulating B1 cell function more directly, we generated mice with B cell-specific loss of CXCR4 (CXCR4BKO). 8-week-old CXCR4BKO mice demonstrate a significant reduction in B1 number in the bone marrow relative to littermate controls (CXCR4WT). No significant changes in B1 number were seen in the aorta, peritoneal cavity, or spleen. Using ELISA and ELISPOT, CXCR4BKO mice were demonstrated to have decreased circulating IgM levels and fewer IgM antibody-secreting cells (ASC) in the bone marrow, but not in spleen. CXCR4BKO and CXCR4WT mice were placed on 9 weeks Western diet (WD) or control chow diet and then analyzed for IgM ASC number. CXCR4WT WD-fed mice have increased IgM ASC’s in the bone marrow relative to CXCR4WTchow-fed controls. This increase did not occur in WD-fed CXCR4BKO mice. Our data demonstrate that CXCR4 mediates B1 localization to the bone marrow and IgM production in mice, and indicate an atheroprotective role for CXCR4 on B1 cells." @default.
- W4313356104 created "2023-01-06" @default.
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- W4313356104 date "2016-05-01" @default.
- W4313356104 modified "2023-09-27" @default.
- W4313356104 title "CXCR4 mediates B-1 cell localization to the bone marrow and production of atheroprotective IgM antibody" @default.
- W4313356104 doi "https://doi.org/10.4049/jimmunol.196.supp.119.21" @default.
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