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Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma

Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene... The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H)- and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (D H) gene segment to a joining (J H) gene segment. This forms a DJ H intermediate to which a variable (V H) gene segment is subsequently added. Light-cháin gene rearrangement follows and consists of the joining of a V L gene segment to a J L gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (slgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation2,3 or possibly by continued recombinational events4. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both λ and H-chain genes subsequent to the formation of slgM (μκ) molecules5. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between V H genes which results in the replacement of most or all of the coding sequence of the initial V HQ52 rearrangement by a germline V H7183 gene. Embedded in the V H coding sequence close to the site of the cross-over is the sequence 5′ TACTGTG 3′, which is identical to the signal heptamer found 5′ of many D H gene segments6. This embedded heptamer is conserved in over 70% of known V H genes7–17. We suggest that this heptamer mediates V H gene replacement and may play an important part in the development of the antibody repertoire. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma

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References (33)

Publisher
Springer Journals
Copyright
Copyright © 1986 by Nature Publishing Group
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/322843a0
Publisher site
See Article on Publisher Site

Abstract

The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H)- and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (D H) gene segment to a joining (J H) gene segment. This forms a DJ H intermediate to which a variable (V H) gene segment is subsequently added. Light-cháin gene rearrangement follows and consists of the joining of a V L gene segment to a J L gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (slgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation2,3 or possibly by continued recombinational events4. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both λ and H-chain genes subsequent to the formation of slgM (μκ) molecules5. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between V H genes which results in the replacement of most or all of the coding sequence of the initial V HQ52 rearrangement by a germline V H7183 gene. Embedded in the V H coding sequence close to the site of the cross-over is the sequence 5′ TACTGTG 3′, which is identical to the signal heptamer found 5′ of many D H gene segments6. This embedded heptamer is conserved in over 70% of known V H genes7–17. We suggest that this heptamer mediates V H gene replacement and may play an important part in the development of the antibody repertoire.

Journal

Nature – Springer Journals

Published: Aug 28, 1986

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