Soluble antigen can cause enhanced apoptosis of germinal-centre B cells.
Germinal centres are dynamic microenvironments of B-lymphocyte differentiation, which develop in secondary lymphoid tissues during immune responses. Within germinal centres, activated B lymphocytes proliferate and point mutations are rapidly introduced into the genes encoding their immunoglobulin receptors. As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen. Immunoglobulin gene mutation can also lead to reactivity to self antigens. It has been suggested that any newly formed self-reactive B cells are eliminated within the germinal centre in order to avoid autoimmunity. 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.
Pulendran
B
B
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Kannourakis
G
G
Nouri
S
S
Smith
K G
KG
Nossal
G J
GJ
D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D003165:Complement System Proteins / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D012709:Serum Albumin / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000941:Antigens; D006241:Haptens; C000715470:MAS1 protein, human; D009596:Nitrophenols; D010648:Phenylacetates; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012709:Serum Albumin; C026242:4-hydroxy-5-nitrophenyl acetic acid; D003165:Complement System Proteins