IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.

Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen se...

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Autores principales:	Yan Wang, Katherine J L Jackson, Janet Davies, Zhiliang Chen, Bruno A Gaeta, Janet Rimmer, William A Sewell, Andrew M Collins
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1f0953652fc401faf7b688831877283
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spelling	oai:doaj.org-article:a1f0953652fc401faf7b6888318772832021-11-18T08:31:06ZIgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.1932-620310.1371/journal.pone.0089730https://doaj.org/article/a1f0953652fc401faf7b6888318772832014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586993/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases. The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset. A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.Yan WangKatherine J L JacksonJanet DaviesZhiliang ChenBruno A GaetaJanet RimmerWilliam A SewellAndrew M CollinsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89730 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yan Wang Katherine J L Jackson Janet Davies Zhiliang Chen Bruno A Gaeta Janet Rimmer William A Sewell Andrew M Collins IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
description	Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases. The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset. A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.
format	article
author	Yan Wang Katherine J L Jackson Janet Davies Zhiliang Chen Bruno A Gaeta Janet Rimmer William A Sewell Andrew M Collins
author_facet	Yan Wang Katherine J L Jackson Janet Davies Zhiliang Chen Bruno A Gaeta Janet Rimmer William A Sewell Andrew M Collins
author_sort	Yan Wang
title	IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
title_short	IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
title_full	IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
title_fullStr	IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
title_full_unstemmed	IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
title_sort	ige-associated ighv genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a1f0953652fc401faf7b688831877283
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IgE-associated IGHV genes from venom and peanut allergic individuals lack mutational evidence of antigen selection.

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