Phosphorylcholine-targeting vaccination reduces experimental atherosclerosis progression by expanding the B1 like specific B cell pool

Abstract

Vaccination with phosphorylcholine (PC) reduces experimental atherosclerosis by raising the titer of PC-specific IgM in Apolipoprotein E knockout (ApoEKO) mice. The epitope of the antibodies elicited by the PC-Vaccine coincides with that of ‘natural’ anti-pneumococcal antibodies and strikingly similar results can be obtained by vaccination with Prevenar®. The aim of the present study was therefore to assess whether the atheroprotective effects carried by PC-Vaccine and Prevenar@ are linked to the activation of the germline encoded B cell pool, which is responsible for the production of natural antibodies. AID Cre mice were crossed with ApoEKO mice and double transgenic mice were immunized with PC-Vaccine or with Prevenar® as previously reported (DOI:10.1016/j.atherosclerosis.2018.06.903). Three months later, atherosclerotic lesions and natural anti-PC IgM antibodies values were compared to the AID+ (affinity maturated) IgM+ (B1-like) cell pool in the peritoneal cavity and draining lymph nodes. Discriminant analysis showed that the rise of natural anti-PC IgM antibodies (AB1-2 IgM), the proportion of affinity matured (AID + ) B1-like cells (CD19+ CD5+ CD43+ CD1d+ IgM + ) having migrated from the draining lymph node to the peritoneal cavity and the lesion size (AUC) were interdependent from each other and that atheroprotection in both PC-Vaccine and Prevenar® mouse groups was proportional to the fraction of affinity matured B1-like cells in the peritoneal cavity and the rise of natural anti-PC IgM antibody production (individual data and bivariate plots are displayed in Fig. 1 ). Phosphorylcholine-targeting vaccination boosts affinity maturation of B lymphocytes involved in the production of natural antibodies and prevents experimental atherosclerosis progression.