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Soluble antigen can cause enhanced apoptosis of germinal-centre B cells


GERMINAL centres are dynamic microenvironments of B-lympho-cyte differentiation, which develop in secondary lymphoid tissues during immune responses1-3. Within germinal centres, activated B lymphocytes proliferate and point mutations are rapidly introduced into the genes encoding their immunoglobulin receptors4-10. As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen4-11. Immunoglobulin gene mutation can also lead to reactivity to self antigens12-14. It has been suggested that any newly formed self-reactive B cells are eliminated within the germinal centre in order to avoid autoimmunity15,16. Here we present evidence that antigen-specific, high-affinity, germinal-centre B cells are rapidly killed by apoptosis in situ when they encounter soluble antigen. The effect seems to act directly on the B cells, rather than through helper T cells. Furthermore, the apoptosis is unique to germinal-centre cells, and is only incompletely impeded by constitutive expression of the proto-oncogene bcl-2. This phenomenon may reflect clonal deletion of self-reactive B cells within germinal centres.

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Pulendran, B., Kannourakis, G., Nouri, S. et al. Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. Nature 375, 331–334 (1995).

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