P604B regulatory cells mediate atheroprotection via IL-10

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Abstract

Background

B cells have been ascribed both atherogenic and atheroprotective properties. These opposing properties may be mediated by diverse B cell subsets. Specific B cell subtypes with suppressive function (Bregs) have not been identified in atherosclerosis. In classic immuno-mediated inflammatory conditions, two main subsets of Bregs have been described. In collagen induced arthritis and experimental lupus like disease, the protective B cell subset express high levels of the surface markers CD1d, CD21, CD23 and CD24. In contact hypersensitivity and experimental autoimmune encephalomyelitis they are CD5 + and express high levels of CD1d. We sought to examine whether regulatory B cells can also be protective in atherosclerosis.

Methods

The proportion of CD1d + CD21high, CD23high CD24high B cells was assessed in lymph nodes and spleen of ApoE-/- mice and compared to wild-type mice by flow cytometry. The effect of adoptive transfer of either whole B cells or specific B cell subsets isolated from spleens and lymph nodes was evaluated in ApoE-/- mice using a perivascular cast-induced model of accelerated atherosclerosis.

Results

Percentages and absolute numbers of CD1d + CD21high, CD23high CD24high B2 cell subset was decreased in the spleens and enriched in the draining lymph nodes of ApoE-/- mice compared to controls at all ages examined. Moreover, transfer of lymph node derived B cells or purified CD1d + CD21high, CD23high CD24high B cells reduced lesion size and macrophage infiltration in lesions without significantly changing serum cholesterol levels. Other subsets of B2 B cells did not confer protection. IL-10 blockade prevented B cell – mediated protection from lesion development.

Conclusions

Our data suggests that CD1d + CD21high, CD23high CD24high B cells arising in lymph node confer protection from the development of vascular lesions. This is the first identification of a specific Breg subset of the B2 lineage with anti atherogenic actions, and it may open the way to novel immunomodulatory approaches in cardiovascular disease.

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