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Convergent evolution and B-cell recirculation in germinal centers in a human lymph node

Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response wit...

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Autores principales: Pelissier, Aurelien, Stratigopoulou, Maria, Donner, Naomi, Dimitriadis, Evangelos, Bende, Richard J, Guikema, Jeroen E, Rodriguez Martinez, Maria, van Noesel, Carel JM
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462906/
https://www.ncbi.nlm.nih.gov/pubmed/37640448
http://dx.doi.org/10.26508/lsa.202301959
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author Pelissier, Aurelien
Stratigopoulou, Maria
Donner, Naomi
Dimitriadis, Evangelos
Bende, Richard J
Guikema, Jeroen E
Rodriguez Martinez, Maria
van Noesel, Carel JM
author_facet Pelissier, Aurelien
Stratigopoulou, Maria
Donner, Naomi
Dimitriadis, Evangelos
Bende, Richard J
Guikema, Jeroen E
Rodriguez Martinez, Maria
van Noesel, Carel JM
author_sort Pelissier, Aurelien
collection PubMed
description Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs.
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spelling pubmed-104629062023-08-30 Convergent evolution and B-cell recirculation in germinal centers in a human lymph node Pelissier, Aurelien Stratigopoulou, Maria Donner, Naomi Dimitriadis, Evangelos Bende, Richard J Guikema, Jeroen E Rodriguez Martinez, Maria van Noesel, Carel JM Life Sci Alliance Research Articles Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs. Life Science Alliance LLC 2023-08-28 /pmc/articles/PMC10462906/ /pubmed/37640448 http://dx.doi.org/10.26508/lsa.202301959 Text en © 2023 Pelissier et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Pelissier, Aurelien
Stratigopoulou, Maria
Donner, Naomi
Dimitriadis, Evangelos
Bende, Richard J
Guikema, Jeroen E
Rodriguez Martinez, Maria
van Noesel, Carel JM
Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title_full Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title_fullStr Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title_full_unstemmed Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title_short Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
title_sort convergent evolution and b-cell recirculation in germinal centers in a human lymph node
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462906/
https://www.ncbi.nlm.nih.gov/pubmed/37640448
http://dx.doi.org/10.26508/lsa.202301959
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