Germinal Center Reaction

Germinal centers (GCs) are transient microstructures formed within the follicles of secondary lymphoid tissues in response to certain types of immunization and foreign pathogens. A mature GC comprises two functionally distinct compartments, a dark zone (DZ) and a light zone (LZ). DZ B cells undergo rapid clonal expansion during which their antibody genes are modified by activation-induced cytidine deaminase (AID)-mediated immunoglobulin variable region (IgV) gene hypermutation to generate a repertoire of antibody mutants with varying affinities to the immunizing antigen. With the help of other immune cells including T follicular helper (Tfh) cells and follicular dendritic cells (FDCs), GC B cells with improved affinity to the antigen are selectively expanded and finally differentiate into memory B cell (MBC) and antibody-producing plasma cell (PC). In the LZ, GC B cells may also undergo AID-mediated class switch recombination. The germinal center reaction involves multiple immune cells and is tightly controlled by lineage-specific transcription factors. In this chapter, I will discuss the cellular and molecular signals, such as key transcription factors, that govern the formation and maintenance and GCs and the selection of GC B cells.