Antigen-receptor junctional diversity in growth-factor-receptor mutant mice.
Precursor lymphocytes undergo expansion prior to immunoglobulin (Ig) or T cell receptor (TCR) rearrangements. Development of thymocytes, but not B cells, is entirely blocked in mice lacking both the receptor-tyrosine-kinase c-kit and the common cytokine receptor gamma chain (gamma c). In c-kit-gamma c-mice, TCR beta rearrangements are limited to mono- or oligoclonal DJ junctions. Here, effects of lack of c-kit or gamma c, or both, on the junctional diversity of TCR gamma and delta, and Ig VH(DH)JH loci were analyzed. All rearrangements were present in wildtype and mutant mice. However, sequencing of the junctions revealed monoclonal TCR gamma (V gamma 2 J gamma 1) and TCR delta (V delta 1(D delta)J delta 2) joints in c-kit-gamma c-, but not c-kit+ gamma c- or wildtype thymocytes. In contrast to TCR beta, gamma and delta loci, VHDHJH junctions were more diverse in c-kit-gamma c-mice. Thus, the two analyzed growth factor receptors mediate signaling pathways required for progenitor expansion and generation of junctional diversity at TCR loci, but have less influence on the diversity of IgH junctions.
Basel Institute for Immunology, Basel, Switzerland. rodewald@bii.ch
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D000818:Animals; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D014644:Genetic Variation; D006133:Growth Substances / Q000502:physiology; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007138:Immunoglobulin delta-Chains / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000502:physiology; D013154:Spleen; D013950:Thymus Gland
D006133:Growth Substances; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains; D007142:Immunoglobulin gamma-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019009:Proto-Oncogene Proteins c-kit