Figure 8.

Proposal of an instructive differentiation model of LZ B_GC-cells integrating the expression of the CD23 marker. B_GC-cells are predominantly CD23^- compete for antigen (Ag) when only limited amount of Ag is available (top-left B cells). Fit cells proliferate, retrieve Ag deposited on follicular dendritic cells (FDCs) and receive survival signals from stromal cells (top-middle part). Note that FDCs express IL-4R and may take available IL-4 cytokine - in a non-directed manner [IL-4 broadcasting as called in (24)] – produced by Tfh. Both, high and low-affinity cells process Ag and present - in proportion to its affinity - peptide-MHC complex which supports the interaction with cognate Tfh and the delivery of crucial molecules including IL-21, CD40L and IL-4 leading to pSTAT6 expression (right-middle part). The split of the B cell fate depends on the integration of sufficient signals which impacts the maintenance or extinction of the IL-4/pSTAT6 signaling pathway. B cells that have quenched the IL-4/STAT6 signal are unable to express the CD23 marker and progress further to the PB axis of differentiation (bottom-right). These CD23^- LZ B_GC-cells correspond to pre-PB described previously (19) which express transiently MYC leading to cell cycle and the committal step of differentiation described elsewhere (14). In contrast, CD23⁺ LZ B_GC-cells which have maintained IL-4/STAT6 signaling are prone to apoptosis or give rise to pre-MBCs; the maintenance of CD23 expression depends on the presence of IL-4 and CD40 stimuli (bottom-middle). In the right square, a view of the Figure 7C concerning scRNA-seq data for B_GC-cells representing the fate of activated LZ B_GC-cells between pre-MBC or PB outputs.