{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:49:01Z","timestamp":1790642941511,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007391","name":"Association pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>B cell affinity maturation occurs in the germinal center (GC). Light-zone (LZ) GC B cells (B<jats:sub>GC<\/jats:sub>-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<jats:sub>GC<\/jats:sub>-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 <jats:italic>PRDM1<\/jats:italic> 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<jats:sub>GC<\/jats:sub>-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<jats:sub>GC<\/jats:sub>-cells were positive. Sorted LZ B<jats:sub>GC<\/jats:sub>-cells left in culture and stimulated upregulated CD23 expression but were unable to differentiate into PCs \u2013 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<jats:sub>GC<\/jats:sub>-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 <jats:italic>MYC<\/jats:italic> gene expression. Overall, the CD23 marker might be of value in answering questions about the differentiation of normal B<jats:sub>GC<\/jats:sub>-cells and allowed us to propose an instructive LZ B<jats:sub>GC<\/jats:sub>-cells maturation and fate model.<\/jats:p>","DOI":"10.3389\/fimmu.2021.744573","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T10:43:57Z","timestamp":1638441837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Committed Human CD23-Negative Light-Zone Germinal Center B Cells Delineate Transcriptional Program Supporting Plasma Cell 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