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 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.
Mi
Q S
QS
Laboratory of Immunology, B Cell Development Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Zhou
L
L
Schulze
D H
DH
Fischer
R T
RT
Lustig
A
A
Rezanka
L J
LJ
Donovan
D M
DM
Longo
D L
DL
Kenny
J J
JJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D003429:Cross Reactions; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D006433:Hemocyanins / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D016056:Immunodominant Epitopes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D014774:Virulence
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin