FIGURE 1.

Genetic lesions associated with distinct transcription and molecular subtypes of DLBCL. Schematic representation of the germinal center (GC) reaction and its relationship with the major molecular and genetic subtypes of DLBCL. The GC forms upon encounter of a naïve B cell with an antigen, and it is divided in two distinct compartments: the dark zone (DZ) and the light zone (LZ). In the GC DZ, B cells freely proliferate and undergo somatic hypermutation. However, signals from the GC LZ induce expression of antigen presentation in B cells, so that high affinity B cells can be selected to exit the GC reaction and terminally differentiate into plasma cells or memory B cells. Cells that are not selected undergo apoptosis. As the B cells repeatedly cycle between DZ and LZ, they might acquire mutations in genes predominantly activated in the different GC phases, translating in a distinct genetic, transcriptional and phenotypic subtype which might shape the surrounding tumor microenvironment.