Review

Cognate interactions between Ag-specific B cells, CD4+ T helper cells, and DCs in response to foreign Ag lead to the formation of germinal centers (GCs). GCs are specialized structures in B cell follicles of secondary lymphoid tissues where somatic hypermutation of Ig variable (V) region genes and selection of high-affinity B cells occur, followed by differentiation of long-lived memory or plasma cells (PC). This process ensures the development of long-lived humoral immunity after infection or vaccination with T cell–dependent (TD) Ag and is a unique fea-ture of the mammalian immune system (Tangye and Tarlinton, 2009; Goodnow et al., 2010). It has been known for decades that CD4