The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21

How IL-21 functions during development of high affinity antibody in germinal centres (GC) is not fully known. Here using a cell cycle reporter mouse, the authors show that IL-21 promotes cell cycle progression within the GC light zone and enables release from the G1 cell cycle stage. Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.