Abstract Signaling through Toll-like receptors (TLR) such as TLR7 and TLR9 has been implicated in B cell activation by self-antigens and development of autoimmunity. Our recent work based on murine models has identified a novel mechanism by which a family of adhesion molecules called αv integrins and the autophagy pathway limit excessive B cell responses to antigens containing TLR ligands and self-derived antigens. Specifically, we have found that αvβ3 integrin regulates B cell TLR signaling by directing trafficking and maturation of TLR containing endosomes and engaging components of the autophagy pathway. When B cells lack either αv integrins or autophagy components LC3 and Atg5 endosomal trafficking of the TLRs is disrupted and leads to enhanced TLR signaling and increased B cell responses. We have used av conditional knockout mice to determine the consequences of loss of this αvβ3-mediated immune regulation. Mice lacking B cell av show increased antibody responses to antigens containing TLR-ligands and develop increased levels of autoantibodies. We therefore propose that αv-mediated TLR regulation serves to maintain the balance between protective immunity to microbes and potential pathological autoimmune responses. We are currently studying the role of αv signaling and autophagy components in development of class switched, high affinity antibodies in response to antigens in the context of infection with a pathogen or in response to self-antigens.