T cells and follicular dendritic cells in germinal center B‐cell formation and selection

Summary:  Germinal centers (GCs) are specialized microenvironments formed after infection where activated B cells can mutate their B‐cell receptors to undergo affinity maturation. A stringent process of selection allows high affinity, non‐self‐reactive B cells to become long‐lived memory B cells and plasma cells. While the precise mechanism of selection is still poorly understood, the last decade has advanced our understanding of the role of T cells and follicular dendritic cells (FDCs) in GC B‐cell formation and selection. T cells and non‐T‐cell‐derived CD40 ligands on FDCs are essential for T‐dependent (TD) and T‐independent GC formation, respectively. TD‐GC formation requires Bcl‐6‐expressing T cells capable of signaling through SAP, which promotes formation of stable T:B conjugates. By contrast, differentiation of B blasts along the extrafollicular pathway is less dependent on SAP. T‐follicular helper (Tfh) cell‐derived CD40L, interleukin‐21, and interleukin‐4 play important roles in GC B‐cell proliferation, survival, and affinity maturation. A role for FDC‐derived integrin signals has also emerged: GC B cells capable of forming an immune synapse with FDCs have a survival advantage. This emerges as a powerful mechanism to ensure death of B cells that bind self‐reactive antigen, which would not normally be presented on FDCs.