B7-1 AND B7-2 HAVE OVERLAPPING, CRITICAL ROLES IN IMMUNOGLOBULIN CLASS SWITCHING AND GERMINAL CENTER FORMATION

Humoral immune responses were characterized in mouse strains lacking e ither or both B7 molecules. Mice deficient in both B7-1 and B7-2 faile d to generate antigen-specific IgG1 and IgG2a responses and lacked ger minal centers when immunized by a number of routes and even in the pre sence of complete Freund's adjuvant. These results demonstrate that B7 -mediated signaling plays a critical role in germinal center formation and immunoglobulin class switching in vivo. Mice lacking only B7-1 or B7-2 mounted high-titer antigen-specific IgG responses when immunized in complete Freund's adjuvant, indicating that B7-1 and B7-2 can have overlapping, compensatory functions for IgG responses. When immunized intravenously without adjuvant, B7-2-deficient mice failed to switch antibody isotypes or form germinal centers, whereas B7-1-deficient mic e gave antibody responses comparable with wild-type mice. Thus, B7-2 h as an important role in initiating antibody responses in the absence o f adjuvant, but the induction of B7-1 by adjuvant in B7-P-deficient mi ce can compensate for the absence of B7-2.