Mechanism of antigen-driven selection in germinal centres

YJ Liu, DE Joshua, GT Williams, CA Smith, J Gordon… - Nature, 1989 - nature.com
YJ Liu, DE Joshua, GT Williams, CA Smith, J Gordon, ICM MacLennan
Nature, 1989nature.com
THE high affinity of antibodies produced during responses to T-cell-dependent antigens is
associated with somatic mutation in the variable region of the immunoglobulin1–4. 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 antigen5. We have now performed …
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 immunoglobulin1–4. 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 antigen5. 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 apoptosis6. 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 antibodies7,8.
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