An allotype linked gene that is associated with a negative or very low anti-phosphorylcholine response (PC) phenotype in wild mice (CNV).
In contrast to most inbred and wild mice, a population of wild mice recently isolated from a farm in Centreville, MD, and designated CNV produced no anti-phosphorylcholine (PC) antibodies (less than 1 microgram/ml) in response to immunization with the PC antigen Streptococcus pneumoniae (R36A) and gave 9 to 36 micrograms/ml anti-PC response to PC-KLH at 14 days after immunization. When another carbohydrate antigen, namely, bacterial levan, was used, CNV mice all gave high antibody titers. When CNV (PC-) mice were bred to inbred C.B20 (PC+) mice, 82% of the F1 and 76% of the F2 hybrids were surprisingly non-responders (PC-), which suggested that PC- gene(s) of CNV origin dominated the response to these antigens. The 18% PC+ phenotype in the F1 hybrids indicated possible heterozygosity of the PC genes controlling the PC- response in the CNV mice. Genetic studies on CNV mouse No. 378 supported this possibility. Analysis of the F2 data strongly suggest that two genes determined the PC- response, one of which was closely linked to the Igh-C allotype locus (chromosome 12). Hypothetically, we propose that CNV mice have two genes that cooperate but that sometimes act independently to express the PC- phenotype. Surprisingly, when F1 mice giving PC- phenotypes were back-crossed to C.B20, very few mice (18%) were PC-. This indicated that the PC- determining genes of CNV origin were not able to dominate immune responses in the presence of a larger number of C.B20 genes. This kind of expression may be regulated by other factors, such as clonotype competition and clonal dominance.
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D002794:Choline / Q000031:analogs & derivatives*; D003433:Crosses, Genetic; D005630:Fructans / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007444:Inulin / Q000276:immunology; D051379:Mice / Q000276:immunology*; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010767:Phosphorylcholine / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology
D000907:Antibodies, Bacterial; D005630:Fructans; D007126:Immunoglobulin Allotypes; D007127:Immunoglobulin Constant Regions; D010767:Phosphorylcholine; D007444:Inulin; D002794:Choline