Allelic exclusion of immunoglobulin gene rearrangement and expression: why and how?
Since the discovery of the allelic exclusion of immunoglobulin (Ig) gene expression by Pervis in the 1960s [J. Exp. Med. 122 (1965) 853], much attention has been focused on its mechanism. Much less attention has been paid, however, to the question of why B cells demonstrate such unusual genetic regulation of antigen receptor gene expression. A large body of literature implicates the Ig gene products as feedback regulators of their own genetic rearrangement [Adv. Immunol.78 (2001)169; Science 236 (1987)816]. While a role for Ig gene products in the regulation of V(D)J recombination is beyond debate, it is extremely unlikely that such a feedback mechanism would be fast enough to avoid occasional near-simultaneous rearrangement of allelic loci leading to dual receptor gene expression. This review will suggest an hypothesis to answer the 'why bother' aspect of allelic exclusion and then go on to propose a mechanism, distinct from feedback regulation, which may contribute to the allelic exclusion of Ig gene expression.
Schlissel
Mark
M
Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720-3200, USA. mss@uclink4.berkeley.edu
D000483:Alleles; D000818:Animals; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D005246:Feedback; D015870:Gene Expression; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D018448:Models, Immunological; D045522:Recombinases
D045522:Recombinases; D004254:DNA Nucleotidyltransferases