Bone marrow-selected antigen specific regulatory B cells

Autoimmunity is often regarded as pathogenic, but this view has gradually shifted over time. Based on insights from thymus selection, T cells are now known to be selected by self-antigens and positive selection in the thymus medulla leads to regulatory functions. B cells are selected in the bone marrow and the fundamental question is whether self-antigens in the bone marrow select antigen specific regulatory B cells. In this work, we show that B cells are indeed selected for proteins expressed in the bone marrow and develop into cells with regulatory function bearing distinct phenotypic fingerprint. Collagen type II specific regulatory B cells trigger the expansion of antigen specific regulatory T cells and protect against development of tissue specific autoimmune inflammation. These antigen specific regulatory B cells constitute a sizeable fraction of the normal B cell repertoire in both mice and humans.