The Germinal Center Reaction

The germinal center (GC) reaction is the basis of T-dependent humoral immunity against foreign pathogens and the ultimate expression of the adaptive immune response. GCs represent a unique collaboration between proliferating antigen-specific B cells, T follicular helper cells, and the specialized follicular dendritic cells that constitutively occupy the central follicular zones of secondary lymphoid organs. The primary function of GCs is to produce the high-affinity antibody-secreting plasma cells and memory B cells that ensure sustained immune protection and rapid recall responses against previously encountered foreign antigens. However, the process of somatic mutation of antibody variable region genes that underpins GC function also carries significant risks in the form of unintended oncogenic mutations and generation of potentially pathogenic autoantibody specificities. Here we review the current knowledge on the recruitment, selection, and differentiation of B cells during GC responses and the implication of defects in GC physiology for autoimmune, inflammatory, and malignant diseases. Recent advances in documenting cellular movement within GCs and some of the key migratory signals responsible for GC formation are also discussed.