High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans

The ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the ma...

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Main Authors: Roy, A, Bystry, V, Bohn, G, Goudevenou, K, Reigl, T, Papaioannou, M, Krejci, A, O'Byrne, S, Chaidos, A, Grioni, A, Darzentas, N, Roberts, I, Karadimitris, A
Format: Journal article
Language:English
Published: Elsevier 2017
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author Roy, A
Bystry, V
Bohn, G
Goudevenou, K
Reigl, T
Papaioannou, M
Krejci, A
O'Byrne, S
Chaidos, A
Grioni, A
Darzentas, N
Roberts, I
Karadimitris, A
author_facet Roy, A
Bystry, V
Bohn, G
Goudevenou, K
Reigl, T
Papaioannou, M
Krejci, A
O'Byrne, S
Chaidos, A
Grioni, A
Darzentas, N
Roberts, I
Karadimitris, A
author_sort Roy, A
collection OXFORD
description The ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the main source of IgM natural immunity during the 2nd trimester. Strikingly, 0.25% of all prenatal clonotypes, comprising 18.7% of the expressed repertoire, are shared with the postnatal samples, consistent with persisting fetal IgM+ B cells being a source of natural IgM repertoire in adult life. Further, the origins of specific stereotypic IgM+ B cell receptors associated with chronic lymphocytic leukemia, can be traced back to fetal B cell lymphopoiesis, suggesting that persisting fetal B cells can be subject to malignant transformation late in life. Overall, these novel data provide unique insights into the ontogeny of physiological and malignant B lymphopoiesis that spans the human lifetime.
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spelling oxford-uuid:8da2807c-db03-4b2c-a7e7-1c4c6d1777452022-03-26T22:52:32ZHigh resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8da2807c-db03-4b2c-a7e7-1c4c6d177745EnglishSymplectic Elements at OxfordElsevier2017Roy, ABystry, VBohn, GGoudevenou, KReigl, TPapaioannou, MKrejci, AO'Byrne, SChaidos, AGrioni, ADarzentas, NRoberts, IKaradimitris, AThe ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the main source of IgM natural immunity during the 2nd trimester. Strikingly, 0.25% of all prenatal clonotypes, comprising 18.7% of the expressed repertoire, are shared with the postnatal samples, consistent with persisting fetal IgM+ B cells being a source of natural IgM repertoire in adult life. Further, the origins of specific stereotypic IgM+ B cell receptors associated with chronic lymphocytic leukemia, can be traced back to fetal B cell lymphopoiesis, suggesting that persisting fetal B cells can be subject to malignant transformation late in life. Overall, these novel data provide unique insights into the ontogeny of physiological and malignant B lymphopoiesis that spans the human lifetime.
spellingShingle Roy, A
Bystry, V
Bohn, G
Goudevenou, K
Reigl, T
Papaioannou, M
Krejci, A
O'Byrne, S
Chaidos, A
Grioni, A
Darzentas, N
Roberts, I
Karadimitris, A
High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title_full High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title_fullStr High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title_full_unstemmed High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title_short High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans
title_sort high resolution igh repertoire analysis reveals fetal liver as the likely origin of life long innate b lymphopoiesis in humans
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