| First Author | Mi QS | Year | 2000 |
| Journal | Proc Natl Acad Sci U S A | Volume | 97 |
| Issue | 11 | Pages | 6031-6 |
| PubMed ID | 10811914 | Mgi Jnum | J:62284 |
| Mgi Id | MGI:1858675 | Doi | 10.1073/pnas.110039497 |
| Citation | Mi QS, et al. (2000) Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse. Proc Natl Acad Sci U S A 97(11):6031-6 |
| abstractText | Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, 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 the V1 H 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 the V1 gene. No anti-PC Abs were produced in V1(-/-) mice immunized with avirulent SPn; 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 virulent SPn; thus, <25% of V1(-/-) mice survived challenge with 10(4) bacteria 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 to SPn proteins that can partially protect mice against SPn. These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn, and the V1(-/-) mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection. |
