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Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome
Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1993
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191178/ https://www.ncbi.nlm.nih.gov/pubmed/8350056 |
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collection | PubMed |
description | Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire. |
format | Text |
id | pubmed-2191178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1993 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21911782008-04-16 Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome J Exp Med Articles Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire. The Rockefeller University Press 1993-09-01 /pmc/articles/PMC2191178/ /pubmed/8350056 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title | Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title_full | Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title_fullStr | Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title_full_unstemmed | Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title_short | Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome |
title_sort | diversification, not use, of the immunoglobulin vh gene repertoire is restricted in digeorge syndrome |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191178/ https://www.ncbi.nlm.nih.gov/pubmed/8350056 |