Innate autoreactive B cells as antigen-presenting cells in the induction of tolerance to conserved keratin polypeptide

Abstract

Innate B cells account for a substantial proportion of total B lymphocytes and express autoreactive B cell receptors directed against self-constituents. However, whether innate autoreactive B cells present auto-antigens to T cells, and if so, whether they trigger an autoimmune response, are unclear. In this study, we have characterized splenic keratin-reactive B cells from naïve mice and investigated their roles in keratin antigen presentation. We observed that splenic keratin-reactive B cells expressed germline encoded VH and VK genes based on Igs from anti-keratin hybridomas. Moreover, they frequently utilized gene segment of DFL16.2 and JK2 in the CDR3 regions of heavy and light chain, suggesting that these cells are probably selected on the basis of the specificity of their BCRs. In the presence of keratin antigen, splenic keratin-reactive B cells stimulated significant IL-2 productions from keratin-specific T hybridomas, which were augmented by increasing the concentration of keratin and the numbers of keratin-reactive B cells. By contrast, keratin-reactive B cells failed to stimulate the proliferations of freshly isolated keratin-specific T cells from lymph nodes. The phenotypic analysis of splenic keratin-reactive B cells indicated that low expressions of B7-1 and B7-2 might be the underlying mechanisms for this incomplete function of B cell presentation. Our experiments indicate that splenic keratin-reactive B cells are ineffective in activating freshly isolated T cells from lymph nodes, suggesting a role for innate autoreactive B cells as antigen-presenting cells in tolerance to self-antigens.