Protective intestinal anti-rotavirus B cell immunity is dependent on alpha(4)beta(7) integrin expression but does not require IgA antibody production

Rotavirus (RV) is the main cause of severe gastroenteritis in young childre n; protection has been correlated with intestinal Ab responses. Using a mou se model of RV infection and beta (7)-deficient (beta (-/-)(7)) mice, which do not express alpha (4)beta (7) integrin, we demonstrated the importance of alpha (4)beta (7) integrin in B cell-mediated anti-RV immunity. beta (-/ -)(7) mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. alpha (4 )beta (-/-)(7) immune B cells did not resolve RV infection when adoptively transferred into RV-infected Rag-2-deficient mice. Fewer RV-specific B cell s were found in the intestine of Rag-2-deficient mice transferred with beta (-/-)(7) B cells compared with wild type. The absence of alpha (4)beta (7) expression and/or a lower frequency of IgA-producing cells among transferr ed beta (-/-)(7) B cells could have accounted for the inability of these ce lls to resolve RV infection following passive transfer, To distinguish betw een 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 tra nsfer of immune IgA(-/-) B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and I gA(-/-) mice that, following oral RV infection, protective B cells reside i n the alpha (4)beta (high)(7) population. Our findings suggest that alpha ( 4)beta (7) integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.