Mechanism of antigen-driven selection in germinal centres.
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.
Liu
Y J
YJ
Department of Immunology, University of Birmingham Medical School, UK.
Joshua
D E
DE
Williams
G T
GT
Smith
C A
CA
Gordon
J
J
MacLennan
I C
IC
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
D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface