1. Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation
- Author
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Santamaria, Kathleen, Desmots, Fabienne, Leonard, Simon, Caron, Gersende, Haas, Marion, Delaloy, Céline, Chatonnet, Fabrice, Rossille, Delphine, Pignarre, Amandine, Monvoisin, Céline, Seffals, Marine, Lamaison, Claire, Cogne, Michel, Tarte, Karin, Fest, Thierry, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], LabEX IGO Immunothérapie Grand Ouest, Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hematology Laboratory (Pple de Biologie, CHU de Rennes, Rennes, France), Association pour la Recherche contre le Cancer (ARC)Fondation ARC pour la Recherche sur le CancerFrench National Research Agency (ANR) [ANR-11-LABX-0016-01, PJA3 2020060002221], [PJA 20181207839], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nantes Université (Nantes Univ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Chard-Hutchinson, Xavier, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID
- Subjects
B-Lymphocytes ,germinal center (GC) B cells ,Transcription, Genetic ,Receptors, IgE ,CD23+B cells ,[SDV]Life Sciences [q-bio] ,Immunology ,Cell Differentiation ,germinal center (GC) ,plasmablasts ,GC Light-Zone B cells ,Germinal Center ,Lymphocyte Activation ,plasma cells ,[SDV] Life Sciences [q-bio] ,CD23+ B cells ,Humans ,B cell differentiation ,plasmablasts/plasma cells ,Original Research - Abstract
International audience; B cell affinity maturation occurs in the germinal center (GC). Light-zone (LZ) GC B cells (B-GC-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 B-GC-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 B-GC-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 B-GC-cells were positive. Sorted LZ B-GC-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 B-GC-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 B-GC-cells and allowed us to propose an instructive LZ B-GC-cells maturation and fate model.
- Published
- 2021