Positively selected LZ B GC-cells escape from apoptosis, upregulate transiently their MYC expression, re-enter the cell cycle and travel to the DZ for further cell division and AID activity ( 7– 9). MBCs tend to emerge earlier from a low-affinity compartment in the LZ, while PCs appear later during the immune response, committed B cells require strong Tfh cell help, and accumulate somatic hypermutation ( 4– 6). Hence, Tfh-derived signals enable B-cell proliferation, differentiation and isotype switching ( 3). Once the Ag is captured by the BCR, the cell receives a survival signal the Ag is subsequently internalized, processed and presented on the cell surface as a class II MHC-peptide complex, which in turn leads to interaction with cognate Tfh cells.
Secondly, the light zone (LZ) mainly contains non-proliferating centrocytes, some of them testing their BCR against the Ags displayed by follicular dendritic cells (FDCs) and thus competing for limited, sequential help from T follicular helper (Tfh) cells ( 1– 3). Firstly, the dark zone (DZ) is close to the T-zone and is where centroblasts proliferate in bursts. Fully developed GCs comprise two functional zones, each of which contains a distinct GC B cell (B GC-cell) subtype. Iterative rounds of proliferation (associated with activation-induced cytidine (AID) enzyme activity) and positive selection of B-cell receptors (BCRs) with high affinity for their cognate antigens (Ags) ultimately lead to the production of memory B cells (MBCs) and plasma cells (PCs). Within the secondary lymphoid organs, the germinal center (GC) is the primary site for the maturation of B-cell affinity. Light-zone GC B cells heterogeneity through use of the CD23 marker allow to decipher gene expression changes during B cell differentiation Introduction Only human light-zone GC B cells that fail to express CD23 after appropriate stimulation are likely to differentiate into plasma cells 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.
#Lightzone extensions Pc
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.
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