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Biomedical subjects

David Nemazee

Publications and source records attributed to David Nemazee.

21 records · Page 2Linked to original sources
PubMed2003

Antigen receptor selection by editing or downregulation of V(D)J recombination.

Clonal selection is central to immune function, but it is complemented by "receptor selection", which regulates the immune repertoire not by cell death or proliferation but through the control of antigen receptor gene recombination. Inappropriate receptors, such as those that are autoreactive, underexpressed, or that fail to promote positive selection of thymocytes or B cells, stimulate secondary V-to-J recombinations that destroy and replace receptor genes. These processes play a central role in lymphocyte repertoire development. Recent work on the role of receptor selection in B and T cells has uncovered evidence for and against antigen-induced editing in thymocytes. Many studies suggest that editing plays a central role in B and T lymphocyte repertoire development. Important recent evidence has been uncovered addressing the role of tolerance-induced editing in thymocytes.

Animals↗
PubMed2002

Haplotype exclusion and receptor editing: irreconcilable differences?

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.

Alleles↗