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Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation

Germinal centers (GC) are microstructures where B cells that have been activated by antigen can improve the affinity of their B cell receptors and differentiate into memory B cells (MBCs) or antibody‐secreting plasma cells. Here, we have addressed the role of activation‐induced deaminase (AID), whic...

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Autores principales: Gómez‐Escolar, Carmen, Serrano‐Navarro, Alvaro, Benguria, Alberto, Dopazo, Ana, Sánchez‐Cabo, Fátima, Ramiro, Almudena R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724673/
https://www.ncbi.nlm.nih.gov/pubmed/36205653
http://dx.doi.org/10.15252/embr.202255000
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author Gómez‐Escolar, Carmen
Serrano‐Navarro, Alvaro
Benguria, Alberto
Dopazo, Ana
Sánchez‐Cabo, Fátima
Ramiro, Almudena R
author_facet Gómez‐Escolar, Carmen
Serrano‐Navarro, Alvaro
Benguria, Alberto
Dopazo, Ana
Sánchez‐Cabo, Fátima
Ramiro, Almudena R
author_sort Gómez‐Escolar, Carmen
collection PubMed
description Germinal centers (GC) are microstructures where B cells that have been activated by antigen can improve the affinity of their B cell receptors and differentiate into memory B cells (MBCs) or antibody‐secreting plasma cells. Here, we have addressed the role of activation‐induced deaminase (AID), which initiates somatic hypermutation and class switch recombination, in the terminal differentiation of GC B cells. By combining single cell transcriptome and immunoglobulin clonal analysis in a mouse model that traces AID‐experienced cells, we have identified a novel subset of late‐prePB cells (L‐prePB), which shares the strongest clonal relationships with plasmablasts (PBs). Mice lacking AID have various alterations in the size and expression profiles of transcriptional clusters. We find that AID deficiency leads to a reduced proportion of L‐prePB cells and severely impairs transitions between the L‐prePB and the PB subsets. Thus, AID shapes the differentiation fate of GC B cells by enabling PB generation from a prePB state.
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spelling pubmed-97246732022-12-08 Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation Gómez‐Escolar, Carmen Serrano‐Navarro, Alvaro Benguria, Alberto Dopazo, Ana Sánchez‐Cabo, Fátima Ramiro, Almudena R EMBO Rep Articles Germinal centers (GC) are microstructures where B cells that have been activated by antigen can improve the affinity of their B cell receptors and differentiate into memory B cells (MBCs) or antibody‐secreting plasma cells. Here, we have addressed the role of activation‐induced deaminase (AID), which initiates somatic hypermutation and class switch recombination, in the terminal differentiation of GC B cells. By combining single cell transcriptome and immunoglobulin clonal analysis in a mouse model that traces AID‐experienced cells, we have identified a novel subset of late‐prePB cells (L‐prePB), which shares the strongest clonal relationships with plasmablasts (PBs). Mice lacking AID have various alterations in the size and expression profiles of transcriptional clusters. We find that AID deficiency leads to a reduced proportion of L‐prePB cells and severely impairs transitions between the L‐prePB and the PB subsets. Thus, AID shapes the differentiation fate of GC B cells by enabling PB generation from a prePB state. John Wiley and Sons Inc. 2022-10-07 /pmc/articles/PMC9724673/ /pubmed/36205653 http://dx.doi.org/10.15252/embr.202255000 Text en © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Gómez‐Escolar, Carmen
Serrano‐Navarro, Alvaro
Benguria, Alberto
Dopazo, Ana
Sánchez‐Cabo, Fátima
Ramiro, Almudena R
Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title_full Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title_fullStr Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title_full_unstemmed Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title_short Single cell clonal analysis identifies an AID‐dependent pathway of plasma cell differentiation
title_sort single cell clonal analysis identifies an aid‐dependent pathway of plasma cell differentiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724673/
https://www.ncbi.nlm.nih.gov/pubmed/36205653
http://dx.doi.org/10.15252/embr.202255000
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