Control by Ig genes of the responsiveness to a neutralization viral B cell epitope.
In the present study, we analyzed the capacity of seven strains of mice to produce Abs against the neutralization poliovirus C3 B cell epitope, chemically or genetically linked to two different carrier proteins (MalE and keyhole limpet hemocyanin) or to recombinant hepatitis B surface Ag particles. Following immunization with these different immunogens, all strains of mice developed high Ab titers against the carrier proteins. However, only four strains of mice developed a significant Ab response against the poliovirus C3 B cell epitope. Indeed, in contrast to BALB/c, DBA/1, DBA/2, and 129 sv mice, C57BL/6, C3H, and CBA/J mice failed to produce anti-C3 Abs after immunization with the various C3 immunogens. Using various H-2 congenic strains on BALB/c or C57BL/10 background, this study clearly showed that the response to the C3 B cell epitope is not controlled by MHC genes. In contrast, analysis of anti-C3 Ab responses in IgH congenic mouse lines on BALB/c or C57BL/6 background demonstrated that the capacity to respond to this B cell epitope is controlled by genes closely linked to V(H) genes. This study therefore represents the first demonstration that the V(H) polymorphism can limit the Ab response to a viral neutralization epitope, and therefore has important implications for vaccine development.
Leclerc
C
C
Unit of Biology of Immunological Regulations, Pasteur Institute, Paris, France.
Martineau
P
P
Charlot
B
B
Delpeyroux
F
F
van der Werf
S
S
Hofnung
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000235:genetics; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D005803:Genes, Immunoglobulin / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D017955:Poliovirus / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D000939:Epitopes; C442540:VP1 protein, Poliovirus