Fig. 2: Different models of fate determination in germinal center (GC) B cells.

Schematic illustrations of four different models that could be involved in the fate determination process of GC B cells. a The asymmetric fate model suggests that interaction with follicular helper T (Tfh) cells induces polarization in GC B cells, which results in the asymmetric division of fate-determining molecules. Daughter cells inheriting BCL-6, IL-21R, and PAX5 will either retain the GC B cell state or join the memory B cells compartment. In contrast, daughter cells receiving MYC and IRF4 undergo differentiation into PCs. b In the instructive fate model, the Tfh cell help gained by the GC B cell directs its fate. A strong degree of help favors PC differentiation, whereas weak help from T cells results in either memory fate or apoptosis. c In the decreasing potential fate model, a cumulative strength of T cell help and B cell receptor (BCR) signaling over time determines the fate of GC B cells. Repeated proliferation cycles gradually reduce the capability of GC B cells to differentiate into memory B cells, leading to increased plasma cells at later time points in GC reactions. d In the integrative fate model, the quality and quantity of T cell help and BCR signaling are all important in fate determination. It explains the preferential differentiation of GC B cells into PCs at late GC time points. MHC Major histocompatibility complex, CD40L CD40 ligand, TCR T cell receptor. Reproduced with permission.