Gene

Cell biology

Memory B cell

Biology

Somatic hypermutation

Germinal center

Receptor

Somatic cell

breakpoint cluster region

Affinity maturation

B cell

Genetics

Antigen

Mutant

Transcription factor

Antibody

Cellular differentiation

Immunological Reviews

Summary Germinal centers (GC) are sites of rapid B‐cell proliferation in response to certain types of immunization. They arise in about 1 week and can persist for several months. In GC s, B cells differentiate in a unique way and begin to undergo somatic mutation of the Ig V regions at a high rate. GC B cells ( GCBC ) thus undergo clonal diversification that can affect the affinity of the newly mutant B‐cell receptor ( BCR ) for its driving antigen. Through processes that are still poorly understood, GCBC with higher affinity are selectively expanded while those with mutations that inactivate the BCR are lost. In addition, at various times during the extended GC reaction, some GCBC undergo differentiation into either long‐lived memory B cells ( MBC ) or plasma cells. The cellular and molecular signals that govern these fate decisions are not well‐understood, but are an active area of research in multiple laboratories. In this review, we cover both the history of this field and focus on recent work that has helped to elucidate the signals and molecules, such as key transcription factors, that coordinate both positive selection as well as differentiation of GCBC .

Linking signaling and selection in the germinal center