B7 requirements for primary and secondary protein- and polysaccharide-specific IG isotype responses to Streptococcus pneumoniae

The requirements for B7 costimulation during an in vivo humoral response to an Intact extracellular bacteria have not been reported. In this study we immunized mice with Streptococcus pneumoniae (R36A) to determine the B7 req uirements for induction of Ig, specific for two determinants on R36A, the p hosphorylcholine (PC) determinant of C-polysaccharide and pneumococcal surf ace protein A (PspA), We show that the primary anti-PspA response, the deve lopment of PspA-specific memory, and the induction of the secondary anti-Ps pA response in primed mice were completely dependent upon B7 costimulation, Of note, costimulation was required only briefly after the secondary immun ization compared with after the primary immunization for optimal induction of Ig, Blockade of B7 costimulation at the time of secondary immunization a lso completely abrogated the established state of memory, but did not induc e tolerance. In contrast to the anti-PspA response, the primary anti-PC res ponse involved only a very short period of B7 costimulation, Whereas B7-2 a lone was required for induction of the primary anti-PspA and anti-PC respon ses, a redundant role for B7-1 and B7-2 was noted for the PspA-specific sec ondary response. CTLA4Ig blocked both the anti-PC and anti-PspA responses e qually well over a wide range of bacterial doses, These studies demonstrate a critical, but variable, role for B7-dependent costimulation during an Ig response to an extracellular bacteria.