T cells and follicular dendritic cells in germinal center B-cell formation and selection.
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.
Vinuesa
Carola G
CG
John Curtin School of Medical Research and Australian Phenomics Facility, Australian National University, Canberra, ACT, Australia. carola.vinuesa@anu.edu.au
Linterman
Michelle A
MA
Goodnow
Chris C
CC
Randall
Katrina L
KL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*