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 β 7-deficient (β 7−/−) mice, which do not express α 4 β 7 integrin, we demonstrated the importance of α 4 β 7 integrin in B cell-mediated anti-RV immunity. β 7−/− mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. α 4 β 7−/− 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 β 7−/− B cells compared with wild type. The absence of α 4 β 7 expression and/or a lower frequency of IgA-producing cells among transferred β 7−/− 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 α 4 β 7 high population. Our findings suggest that α 4 β 7 integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.