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

B Pulendran, G Kannourakis, S Nouri, KGC Smith… - Nature, 1995 - nature.com
B Pulendran, G Kannourakis, S Nouri, KGC Smith, GJV Nossal
Nature, 1995nature.com
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 …
Abstract
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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