ANTIGEN-RECEPTOR JUNCTIONAL DIVERSITY IN GROWTH-FACTOR-RECEPTOR MUTANT MICE

Precursor lymphocytes undergo expansion prior to immunoglobulin (Ig) o r T cell receptor (TCR) rearrangements. Development of thymocytes, but not B cells, is entirely blocked in mice lacking both the receptor-ty rosine-kinase c-kit and the common cytokine receptor gamma chain (gamm a(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 o r gamma(c), or both, on the junctional diversity of TCR gamma and delt a, and Ig V-H(D-H)J(H) loci were analyzed. All rearrangements were pre sent 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, gam ma and delta loci, V(H)D(H)J(H) junctions were more diverse in c-kit(- )gamma(c)(-)mice. Thus, the two analyzed growth factor receptors media te signaling pathways required for progenitor expansion and generation of junctional diversity at TCR loci, but have less influence on the d iversity of IgH junctions. (C) 1998 Elsevier Science Ltd. All rights r eserved.