Protective Intestinal Anti-Rotavirus B Cell Immunity Is Dependent on α4β7 Integrin Expression But Does Not Require IgA Antibody Production

Abstract

Rotavirus (RV) is the main cause of severe gastroenteritis in young children; protection has been correlated with intestinal Ab responses. Using a mouse model of RV infection and β7-deficient (β7−/−) mice, which do not express α4β7 integrin, we demonstrated the importance of α4β7 integrin in B cell-mediated anti-RV immunity. β7−/− mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. α4β7−/− immune B cells did not resolve RV infection when adoptively transferred into RV-infected Rag-2-deficient mice. Fewer RV-specific B cells were found in the intestine of Rag-2-deficient mice transferred with β7−/− B cells compared with wild type. The absence of α4β7 expression and/or a lower frequency of IgA-producing cells among transferred β7−/− B cells could have accounted for the inability of these cells to resolve RV infection following passive transfer. To distinguish between these possibilities, we studied the importance of IgA production in RV infection using IgA-deficient (IgA−/−) mice. IgA−/− mice depleted of CD8+ T cells were able to clear primary RV infection. Similarly, adoptive transfer of immune IgA−/− B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and IgA−/− mice that, following oral RV infection, protective B cells reside in the α4β7high population. Our findings suggest that α4β7 integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.