Figure 1.

Pathways leading to the development of B cell memory. Upon encounter with antigen, activated B cells in secondary lymphoid tissue receive helper signals from cognate CD4⁺ T cells at the border of the B cell follicle and T cell zones. Some of the proliferating B cells differentiate into short-lived plasmablasts that initiate an extrafollicular antibody response, some develop into early memory B cells independently of GC formation, while others aggregate into the follicle to establish a GC. Within the GC, B cells undergo proliferation and somatic hypermutation in the dark zone, followed by affinity-based selection in the light zone with the help of T follicular helper cells and follicular dendritic cells. Long-lived plasma cells and memory B cells emerge from the GC reaction. Upon antigen rechallenge, memory B cells lacking expression of the surface molecules CD80 and PD-L2, mainly of the IgM isotype, can seed secondary GCs, whereas those expressing both molecules, comprising of IgM and IgG isotypes, predominantly generate plasmablasts. GC, germinal center; DC, dendritic cell; SHM, somatic hypermutation.