Haplotype exclusion and receptor editing: irreconcilable differences?

Published

Journal Article (Review)

Features of antibody genes and their regulation hinder two properties thought to be critical for clonal selection: haplotype exclusion and receptor diversity. These properties include: (1) the retention of multiple independent L-chain isotypes, which compounds the problem of allelic exclusion with one of isotype exclusion; (2) the process of receptor editing, in which recombination continues in cells already expressing antigen receptors; and (3) non-random associations and quasi-ordered rearrangements of the elements that generate light chain genes, which promote editing at the expense of allelic exclusion and receptor diversification. In contrast, heavy chain gene structure seems to promote haplotype exclusion and receptor diversity. It appears that requirements of receptor selection, such as the need for receptor editing as an immune tolerance mechanism and positive selection as a quality control checkpoint for receptor functionality, impose independent selections that shape the organization and regulation of the antibody genes. Despite these features, B cell development still achieves a significant level of phenotypic haplotype exclusion, suggesting that there is indeed significant selection for antibody monospecificity that is accommodated along with receptor editing. Thus, the immune system achieves both receptor selection and clonal selection, despite their partly antagonistic mechanisms.

Full Text

Duke Authors

Cited Authors

  • Nemazee, D; Mårtensson, A; Verkoczy, L

Published Date

  • June 2002

Published In

Volume / Issue

  • 14 / 3

Start / End Page

  • 191 - 198

PubMed ID

  • 12160646

Pubmed Central ID

  • 12160646

International Standard Serial Number (ISSN)

  • 1044-5323

Digital Object Identifier (DOI)

  • 10.1016/s1044-5323(02)00042-8

Language

  • eng

Conference Location

  • England