title: Regulation of germinal center B-cell differentiation.
abstract: Germinal centers (GC) are the main sites where antigen-activated B-cell clones expand and undergo immunoglobulin gene hypermutation and selection. Iterations of this process will lead to affinity maturation, replicating Darwinian evolution on the cellular level. GC B-cell selection can lead to four different outcomes: further expansion and evolution, apoptosis (non-selection), or output from the GC with differentiation into memory B cells or plasma cells. T-helper cells in GC have been shown to have a central role in regulating B-cell selection by sensing the density of major histocompatibility complex (MHC):peptide antigen complexes. Antigen is provided on follicular dendritic cells in the form of immune complex. Antibody on these immune complexes regulates antigen accessibility by shielding antigen from B-cell receptor access. Replacement of antibody on immune complexes by antibody generated from GC-derived plasma cell output will gradually reduce the availability of antigen. This antibody feedback can lead to a situation where a slow rise in selection stringency caused by a changing environment leads to directional evolution toward higher affinity antibody.
authors: Institute for Immunology and Immunotherapy, University of Birmingham Medical School, Birmingham, UK.
authors: Yang
authors: Y
authors: Zhang
authors: Institute for Immunology and Immunotherapy, University of Birmingham Medical School, Birmingham, UK.
authors: Laura
authors: L
authors: Garcia-Ibanez
authors: Institute for Immunology and Immunotherapy, University of Birmingham Medical School, Birmingham, UK.
authors: Kai-Michael
authors: KM
authors: Toellner
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation; D060966:Clonal Selection, Antigen-Mediated; D018858:Germinal Center / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D056747:Immunomodulation; D008213:Lymphocyte Activation; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology
keywords: B-cell selection; Tfh cells; affinity maturation; cytokines; germinal center; immune complex