Role of inhibitory B cell co‐receptors in B cell self‐tolerance to non‐protein antigens*

Abstract Antibodies to non‐protein antigens such as nucleic acids, polysaccharides, and glycolipids play important roles in both host defense against microbes and development of autoimmune diseases. Although non‐protein antigens are not recognized by T cells, antibody production to non‐protein antigens involve T cell–independent mechanisms such as signaling through TLR7 and TLR9 in antibody production to nucleic acids. Although self‐reactive B cells are tolerized by various mechanisms including deletion, anergy, and receptor editing, T cell tolerance is also crucial in self‐tolerance of B cells to protein self‐antigen because self‐reactive T cells induce autoantibody production to these self‐antigens. However, presence of T cell–independent mechanism suggests that T cell tolerance is not able to maintain B cell tolerance to non‐protein self‐antigens. Lines of evidence suggest that B cell response to non‐protein self‐antigens such as nucleic acids and gangliosides, sialic acid‐containing glycolipids, are suppressed by inhibitory B cell co‐receptors CD72 and Siglec‐G, respectively. These inhibitory co‐receptors recognize non‐protein self‐antigens and suppress BCR signaling induced by these antigens, thereby inhibiting B cell response to these self‐antigens. Inhibitory B cell co‐receptors appear to be involved in B cell self‐tolerance to non‐protein self‐antigens that can activate B cells by T cell–independent mechanisms.