Dotted line represent the mean value of positive cells for all clusters (last barplot named All_cells) (Chi2 test for each population vs. (B) Distribution of FCER2 + (red) and FCER2 -(black) non-proliferating LZ B GC -cells, in the 12 clusters. and expression of FCER2 in these clusters. (A) UMAP of the 12 specific clusters defined by Holmes et al. (A, B) Single-cell RNA-seq data for human tonsil-derived CXCR4 lo CD83 hi LZ B GCcells in the G0-G1 phase of the cell cycle, from Holmes et al., 2020. | FCER2/CD23 expression delineates specific LZ B GC -cell subsets. 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. In particular, we identified a B cell proliferation signature supported by a transient MYC gene 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. 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. 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. Here, we studied the fate of human LZ B GC -cells as a function of their CD23 expression. Human PC precursors are characterized by the loss of IL-4/STAT6 signaling and the absence of CD23 expression. 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. 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.
B cell affinity maturation occurs in the germinal center (GC).
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