Fetal-derived young B-1 cells prevent atherosclerosis progression in clonal hematopoiesis mouse model

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B591
Abstract ID: 7972

Presenting Author:
Momoko Yoshimoto , Associate Professor at Western Michigan Univ. Homer Stryker MD Sch. of Med.

Abstract:

B-1 cells, an innate-immune-like B-cell subset, mainly develop from fetal progenitors. B-1 cells secrete natural IgM antibodies (NAbs), which bind Oxidized-LDL (oxLDL) that is expressed in the atherosclerotic lesion and apoptotic cells. Therefore, NAbs secreted by B-1 cells clear apoptotic cells and cell debris and play key roles in preventing atherosclerosis and chronic inflammation caused by aging (inflammaging).

Ldlr^-/- mice transplanted with clonal hematopoiesis (CH) bone marrow cells (Tet2^-/- mouse bone marrow) on high-fat diets are an advanced model that reflects the status of human patients with severe atherosclerosis and CH. It has been reported that CH is observed at least 10 % of people older than 70 years and increases the risk of atherosclerotic cardiovascular diseases (CVD). We hypothesize that fetal-derived young B-1 cells prevent the progression of atherosclerosis in CH mice by secreting NAbs that reduce chronic inflammation and that aging of B-1 cells may alter their function. Indeed, our results demonstrated that young B-1 cell injection successfully reduced atherosclerotic lesions in CH mice and that the ability of anti-PC IgM antibody secretion was reduced in CH mice.

Our data showed the critical role of fetal-derived B-1 cells in adult mice and the possibility that the alteration of B-1 cell function causes age-associated diseases.