Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse

Phosphocholine (PC) is the immunodominant epitope found on the surface ofStreptococcus pneumoniae(SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by theV1gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than theV1H chain to protect against pneumococcal infection remains controversial. We generated V1−/−knockout mice to determine whether protective anti-PC Abs could be produced in the absence of theV1gene. No anti-PC Abs were produced in V1−/−mice immunized with avirulentSPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection against virulentSPn; thus, −/−mice survived challenge with 104bacteria as compared with 100% survival of V1+/+mice. The anti-PC Abs in V1−/−mice were heteroclitic, binding to nitrophenyl-PC better than to PC. None of nine hybridomas produced from V1−/−mice provided passive protection. However, the V1−/−mice produced normal amounts of Ab toSPnproteins that can partially protect mice againstSPn. These data indicate that theV1gene is critical for the production of anti-PC Abs providing optimum protection against infection withSPn, and the V1−/−mice could be useful in unmasking epitopes other than the immunodominant PC epitope onSPncapable of providing cross protection.