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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:2a37c82726ad4a66bf158171a125e4262021-12-02T10:42:58ZCommitted Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell Differentiation1664-322410.3389/fimmu.2021.744573https://doaj.org/article/2a37c82726ad4a66bf158171a125e4262021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.744573/fullhttps://doaj.org/toc/1664-3224B 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.Kathleen SantamariaFabienne DesmotsFabienne DesmotsSimon LeonardSimon LeonardGersende CaronGersende CaronMarion HaasMarion HaasCéline DelaloyFabrice ChatonnetFabrice ChatonnetDelphine RossilleDelphine RossilleAmandine PignarreAmandine PignarreCéline MonvoisinMarine SeffalsClaire LamaisonMichel CognéMichel CognéKarin TarteKarin TarteThierry FestThierry FestFrontiers Media S.A.articlegerminal center (GC)germinal center (GC) B cellsCD23+ B cellsB cell differentiationplasmablasts/plasma cellsGC Light-Zone B cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
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| collection |
DOAJ |
| language |
EN |
| topic |
germinal center (GC) germinal center (GC) B cells CD23+ B cells B cell differentiation plasmablasts/plasma cells GC Light-Zone B cells Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
germinal center (GC) germinal center (GC) B cells CD23+ B cells B cell differentiation plasmablasts/plasma cells GC Light-Zone B cells Immunologic diseases. Allergy RC581-607 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
committed human cd23-negative light-zone germinal center b cells delineate transcriptional program supporting plasma cell differentiation |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/2a37c82726ad4a66bf158171a125e426 |
| work_keys_str_mv |
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