Fig. 2

BCR in B cell development. In the bone marrow, progenitor B (pro-B) cells undergo the rearrangement and development of immunoglobulin heavy-chain variable (V), diversity (D), and joining (J) gene segments to form the pre-BCR. The pre-BCR is an immature form of the BCR providing signals for survival, proliferation, and cellular differentiation. After light-chain gene rearrangement occurs, immature B cells express BCR, leave the bone marrow, and mature in the periphery. Mature B cells undergo somatic hypermutation (SHM) driven by the expression of activation-induced cytidine deaminase (AID) in the germinal center (GC) to complete BCR affinity maturation and antibody diversification. The genotoxic stress induced by SHM may lead to the apoptosis of these B cells. However, the continuous BCR signaling could provide pro-survival signals for these B cells, thereby preventing them from apoptosis. Therefore, B cells deficient in Bruton tyrosine kinase tend to undergo apoptosis during the development. The B cells that have completed affinity maturation and antibody diversification then undergo class-switch recombination (CSR), after which they develop into memory B cells with high-affinity BCRs or plasma cells secreting antibodies. DZ, dark zone; LZ, light zone; FDC, follicular dendritic cell; Tfh cell, T follicular helper cell