Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation
B cell affinity maturation occurs in the germinal center (GC). Light-zone (LZ) GC B cells (BGC-cells) interact with follicular dendritic cells (FDCs) and compete for the limited, sequential help from T follicular helper cells needed to escape from apoptosis and complete their differentiation. The hi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.744573/full |
| _version_ | 1818721178584350720 |
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| author | Kathleen Santamaria Fabienne Desmots Fabienne Desmots Simon Leonard Simon Leonard Gersende Caron Gersende Caron Marion Haas Marion Haas Céline Delaloy Fabrice Chatonnet Fabrice Chatonnet Delphine Rossille Delphine Rossille Amandine Pignarre Amandine Pignarre Céline Monvoisin Marine Seffals Claire Lamaison Michel Cogné Michel Cogné Karin Tarte Karin Tarte Thierry Fest Thierry Fest |
| author_facet | Kathleen Santamaria Fabienne Desmots Fabienne Desmots Simon Leonard Simon Leonard Gersende Caron Gersende Caron Marion Haas Marion Haas Céline Delaloy Fabrice Chatonnet Fabrice Chatonnet Delphine Rossille Delphine Rossille Amandine Pignarre Amandine Pignarre Céline Monvoisin Marine Seffals Claire Lamaison Michel Cogné Michel Cogné Karin Tarte Karin Tarte Thierry Fest Thierry Fest |
| author_sort | Kathleen Santamaria |
| collection | DOAJ |
| description | B cell affinity maturation occurs in the germinal center (GC). Light-zone (LZ) GC B cells (BGC-cells) interact with follicular dendritic cells (FDCs) and compete for the limited, sequential help from T follicular helper cells needed to escape from apoptosis and complete their differentiation. The highest-affinity LZ BGC-cells enter the cell cycle and differentiate into PCs, following a dramatic epigenetic reorganization that induces transcriptome changes in general and the expression of the PRDM1 gene in particular. Human PC precursors are characterized by the loss of IL-4/STAT6 signaling and the absence of CD23 expression. Here, we studied the fate of human LZ BGC-cells as a function of their CD23 expression. We first showed that CD23 expression was restricted to the GC LZ, where it was primarily expressed by FDCs; less than 10% of tonsil LZ BGC-cells were positive. Sorted LZ BGC-cells left in culture and stimulated upregulated CD23 expression but were unable to differentiate into PCs – in contrast to cells that did not upregulate CD23 expression. An in-depth analysis (including single-cell gene expression) showed that stimulated CD23-negative LZ BGC-cells differentiated into plasmablasts and time course of gene expression changes delineates the transcriptional program that sustains PC differentiation. In particular, we identified a B cell proliferation signature supported by a transient MYC gene expression. Overall, the CD23 marker might be of value in answering questions about the differentiation of normal BGC-cells and allowed us to propose an instructive LZ BGC-cells maturation and fate model. |
| first_indexed | 2024-12-17T20:34:36Z |
| format | Article |
| id | doaj.art-2a37c82726ad4a66bf158171a125e426 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T20:34:36Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2a37c82726ad4a66bf158171a125e4262022-12-21T21:33:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.744573744573Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell DifferentiationKathleen Santamaria0Fabienne Desmots1Fabienne Desmots2Simon Leonard3Simon Leonard4Gersende Caron5Gersende Caron6Marion Haas7Marion Haas8Céline Delaloy9Fabrice Chatonnet10Fabrice Chatonnet11Delphine Rossille12Delphine Rossille13Amandine Pignarre14Amandine Pignarre15Céline Monvoisin16Marine Seffals17Claire Lamaison18Michel Cogné19Michel Cogné20Karin Tarte21Karin Tarte22Thierry Fest23Thierry Fest24UMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FranceLabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FranceUniversity of Rennes 1, UMS Biosit, H2P2 Platform, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceUMR 1236, University of Rennes 1, INSERM, Établissement Français du Sang Bretagne, Rennes, FrancePôle de Biologie, Rennes University Medical Center, Rennes, FranceB cell affinity maturation occurs in the germinal center (GC). Light-zone (LZ) GC B cells (BGC-cells) interact with follicular dendritic cells (FDCs) and compete for the limited, sequential help from T follicular helper cells needed to escape from apoptosis and complete their differentiation. The highest-affinity LZ BGC-cells enter the cell cycle and differentiate into PCs, following a dramatic epigenetic reorganization that induces transcriptome changes in general and the expression of the PRDM1 gene in particular. Human PC precursors are characterized by the loss of IL-4/STAT6 signaling and the absence of CD23 expression. Here, we studied the fate of human LZ BGC-cells as a function of their CD23 expression. We first showed that CD23 expression was restricted to the GC LZ, where it was primarily expressed by FDCs; less than 10% of tonsil LZ BGC-cells were positive. Sorted LZ BGC-cells left in culture and stimulated upregulated CD23 expression but were unable to differentiate into PCs – in contrast to cells that did not upregulate CD23 expression. An in-depth analysis (including single-cell gene expression) showed that stimulated CD23-negative LZ BGC-cells differentiated into plasmablasts and time course of gene expression changes delineates the transcriptional program that sustains PC differentiation. In particular, we identified a B cell proliferation signature supported by a transient MYC gene expression. Overall, the CD23 marker might be of value in answering questions about the differentiation of normal BGC-cells and allowed us to propose an instructive LZ BGC-cells maturation and fate model.https://www.frontiersin.org/articles/10.3389/fimmu.2021.744573/fullgerminal center (GC)germinal center (GC) B cellsCD23+ B cellsB cell differentiationplasmablasts/plasma cellsGC Light-Zone B cells |
| spellingShingle | Kathleen Santamaria Fabienne Desmots Fabienne Desmots Simon Leonard Simon Leonard Gersende Caron Gersende Caron Marion Haas Marion Haas Céline Delaloy Fabrice Chatonnet Fabrice Chatonnet Delphine Rossille Delphine Rossille Amandine Pignarre Amandine Pignarre Céline Monvoisin Marine Seffals Claire Lamaison Michel Cogné Michel Cogné Karin Tarte Karin Tarte Thierry Fest Thierry Fest Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation Frontiers in Immunology germinal center (GC) germinal center (GC) B cells CD23+ B cells B cell differentiation plasmablasts/plasma cells GC Light-Zone B cells |
| title | Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation |
| title_full | Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation |
| title_fullStr | Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation |
| title_full_unstemmed | Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation |
| title_short | Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation |
| title_sort | committed human cd23 negative light zone germinal center b cells delineate transcriptional program supporting plasma cell differentiation |
| topic | germinal center (GC) germinal center (GC) B cells CD23+ B cells B cell differentiation plasmablasts/plasma cells GC Light-Zone B cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.744573/full |
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