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Genetic mechanisms for dominant V[sub H] gene expression: The V[sub H]B512 gene

Journal Article · · Journal of Immunology; (United States)
OSTI ID:7009495
A total of 37 mAb with reactivity for dextran B512 have been studied; 30 of them were products of independent rearrangements and 21 made use of the same V[sub H] gene, the V[sub H]B512 gene. These results unambiguously established that the immune response to dextran in the high responder mouse strain C57BL/6 was restricted. Idiotypic determinants are located all over the Ig V region. Many but not all Id described so far can be ascribed to protein structures encoded by V[sub H] or V[sub L] gene segments. The expression of the major Id, 17-9 Id, in C57BL/6 was not absolutely correlated with the expression of the dominant V[sub H]B512 gene in the same mouse strain. Inspection of amino acid sequences of the CDR3 of idiotypic positive and negative clones suggested idiotypic structures may be associated with the expression of Tyr at position 95 and Phe or Leu at position 96 in the H and L chains, respectively. Therefore the indiscriminate use of idiotypic markers to characterize V[sub H] genes and the relevance of idiotypic regulation in V[sub H] gene expression are questioned. Id-positive and Id-negative clones displayed similar affinity values for dextran, indicating that idiotypic and binding structures were probably separated. The exchange of Asp65 for Gly65 in one of the clones reduced affinity for dextran, suggesting the involvement of CDR2 in dextran binding. The dominant expression of V[sub H] genes can be explained by somatic and/or genetic mechanisms. Because somatic mechanisms such as idiotypic regulation or selection based on affinity for dextran did not seem to influence the expression of the V[sub H]B512 gene, the authors favor a genetic alternative. They discuss a model based on the distance between V[sub H] genes and D and J[sub H] elements. This model is compatible with somatic and genetic regulation in other systems and provides a new theoretical approach to the understanding of immune V[sub H] dominance and low responsiveness. 43 refs., 3 figs., 4 tabs.
OSTI ID:
7009495
Journal Information:
Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 149:7; ISSN 0022-1767; ISSN JOIMA3
Country of Publication:
United States
Language:
English