Protective Intestinal Anti-Rotavirus B Cell Immunity Is Dependent on alpha sub(4) beta sub(7) Integrin Expression But Does Not Require IgA Antibody Production

• Published in: The Journal of immunology (1950) 2001-02, Vol.166 (3), p.1894-1902
• Main Authors: Kuklin, NA, Rott, L, Feng, Ningguo, Conner, ME, Wagner, N, Mueller, W, Greenberg, H B
• Format: Article
• Language: English
• Subjects: rotavirus
• ISSN: 0022-1767

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 beta sub(7)-deficient ( beta sub(7) super(-/-)) mice, which do not express alpha sub(4) beta sub(7) integrin, we demonstrated the importance of alpha sub(4) beta sub(7) integrin in B cell-mediated anti-RV immunity. beta sub(7) super(-/-) mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. alpha sub(4) beta sub(7) super(-/-) 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 beta sub(7) super(-/-) B cells compared with wild type. The absence of alpha sub(4) beta sub(7) expression and/or a lower frequency of IgA-producing cells among transferred beta sub(7) super(-/-) 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 super(-/-)) mice. IgA super(-/-) mice depleted of CD8 super(+) T cells were able to clear primary RV infection. Similarly, adoptive transfer of immune IgA super(-/-) B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and IgA super(-/-) mice that, following oral RV infection, protective B cells reside in the alpha sub(4) beta sub(7) super(high) population. Our findings suggest that alpha sub(4) beta sub(7) integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.