Differential expression of sets of highly homologous variable region gene products in selected and preimmune repertoires of inbred mouse strains

Using mAb that selectively recognize the various allelic forms of the VHT15 and Vk21D-E genes' products, we analyzed the influence of VH and Vk polymorphism on the probability of expression of these gene segments. Our data show that the frequency to which the VHT15 gene product becomes available in the preimmune repertoire is strongly influenced by the polymorphism of the relevant structural gene, suggesting therefore that VH genes cannot be randomly used in the various strains. Contrary to this, the frequency of Vk21D-E+ clones is similar in all mouse strains tested, and in all cases is higher than the frequency of VHT15 clones. This observation strongly suggests that Vk genes can be randomly expressed, and/or that their number is lower than that of their VH counterpart. Finally, analysis of the specificity associated to the expression of the VHT15 segment revealed that VH polymorphism strongly influences not only the probability of expression of each V gene, but also the specificity of the antibodies on which these VH genes are used.