Leukocyte Bim deficiency does not impact atherogenesis in ldlr ^-/- mice, despite a pronounced induction of autoimmune inflammation.

ABSTRACT: Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim ^-/- or wild type bone marrow transplanted ldlr ^-/- mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim ^-/- transplanted mice displayed splenomegaly and overt lymphocytosis. CD4⁺ and CD8⁺ T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim ^-/- mice. Bim ^-/- mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim ^-/- mice.

SUBMITTER: Temmerman L 

PROVIDER: S-EPMC5465223 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature