Figure 1.
Cell fate decisions in the germinal center (GC) and derived lymphomas. Transient GCs are formed by antigen‐activated mature B cells. (1) In the dark zone, GC B cells proliferate and undergo somatic hypermutation to mutate their immunoglobulin genes. (2) GC B cells transit from the dark zone to the light zone after having divided a determined number of times. (3) In the light zone, cells are selected based on their affinity for the encountered antigen, through their interaction with follicular dendritic cells (FDCs) and follicular T‐helper cells (TFH). (4) After positive selection, cells can concomitantly activate MYC and mTORC1 anabolic programs to grow in size and recycle back to the dark zone for further mutation and clonal expansion. (5) Selected cells can also exit the GC and differentiate into plasma cells (PC) via the intermediary plasmablast (PB) stage, or (6) differentiate into memory B (MB) cells. (7) Cells that are not selected in the light zone or that are damaged during somatic hypermutation in the dark zone undergo apoptosis. Mutual exclusion of BCL6 expression or activity with MYC/mTORC1 reflects commitment to proliferation vs anabolism and recycling. With IRF4/PRDM1 it reflects maintenance of GC identity vs GC exit through differentiation into PC. The putative relation of GC‐derived B‐cell lymphomas and DLBCL subtypes with their respective GC cell‐of‐origin, based on transcriptional and genetic profiles and other characteristics, is shown. Note that C1/BN2 cases resemble marginal zone B cells and that the C5/MCD cases are similar to the extranodal forms of DLBCL