title: Mechanism of antigen-driven selection in germinal centres.
abstract: The high affinity of antibodies produced during responses to T-cell-dependent antigens is associated with somatic mutation in the variable region of the immunoglobulin. Indirect evidence indicates that: (1) this arises by a process of hypermutation, acting selectively on rearranged immunoglobulin variable-region genes, which is activated in centroblasts within germinal centres; and (2) centrocytes, the progeny of centroblasts, undergo selection on the basis of their ability to receive a positive signal from antigen. We have now performed experiments analysing this selection process, and found that, on culture, centrocytes isolated from human tonsil kill themselves within a few hours by apoptosis. This is not a feature of other tonsillar B cells. Centrocytes can be prevented from entering apoptosis if they are activated both through their receptors for antigen and a surface glycoprotein recognized by CD40 antibodies.
authors.affiliation: Department of Immunology, University of Birmingham Medical School, UK.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liu
authors.forename: D E
authors.initials: DE
authors.lastname: Joshua
authors.forename: G T
authors.initials: GT
authors.lastname: Williams
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Gordon
authors.forename: I C
authors.initials: IC
authors.lastname: MacLennan
mesh_terms: D000906:Antibodies / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D003602:Cytotoxicity, Immunologic; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010641:Phenotype
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface