β7 integrin controls immunogenic and tolerogenic mucosal B cell responses

Abstract

IgA production in the gut-associated lymphoid tissue represents a pivotal defense mechanism against luminal pathogens. The other important challenge for the GALT is the induction of local and systemic hyporesponsiveness (tolerance) to dietary antigens and luminal bacterial flora to prevent allergies or deleterious immunologic reactions to food or environmental antigens. In this study we analyzed the impact of β7 integrin on immunogenic and tolerogenic B cell responses in the gastrointestinal tract. β7 integrin deficient mice failed to mount a normal intestinal IgA response to ovalbumin and cholera toxin, whereas the IgG response was unchanged in comparison to control mice. Oral B cell tolerance to ovalbumin, measured as the suppression of specific serum IgG responses, did not develop in the absence of β7 integrin. After adoptive transfer of spleen cells from β7 integrin +/+ mice into RAG-2 deficient or RAG-2/β7 integrin double deficient mice, only RAG-2 deficient mice were able to develop oral B cell tolerance. These observations suggest that β7 integrin expression on cells of the innate immune system contributes to the critical role of β7 integrin in the process of B cell tolerance.