B cell memory: building two walls of protection against pathogens

摘要

In phase 1 of the primary response (left), naive B cells exit the circulation, enter B cell follicles in the secondary lymphoid organ and survey the environment for antigen. Antigens encountered on follicular dendritic cells (FDCs) activate B cells through the B cell receptor (BCR), and the antigens are processed and presented to T cells at the T cell–B cell border, driving naive B cells to proliferate and differentiate into three main cell types: germinal centre (GC)-independent memory B cells, GC B cells or short-lived plasma cells. In phase 2 of the primary response (right), newly differentiated GC B cells form GCs and undergo proliferation and somatic hypermutation in the dark zone before exiting to the light zone, where the GC B cells encounter antigen on FDCs, present the antigen to T follicular helper cells (T cells) and undergo three main fates: namely, differentiation into memory B cells, differentiation into long-lived plasma cells or re-entry into the GC dark zone. In the secondary response (bottom right), memory B cells respond to antigen and differentiate into long-lived plasma cells or GC B cells that undergo GC reactions. TCR, T cell receptor.