Bcl-2 maintains B cell memory.
The number of lymphocytes in an animal is remarkably constant despite antigen-driven proliferation and a high rate of B-cell lymphopoiesis. This reflects the relatively brief lifespan of many newly generated B cells and argues for a well-regulated death mechanism. Even so, a secondary immune response can be generated years after a primary exposure to antigen. Antigen that might restimulate B cells persists for extended periods on follicular dendritic cells in the light zone of germinal centres. Antigen-binding B cells have also been found months after the end of obvious cell division. The precise signal that enables certain B cells to emerge as long-term surviving memory cells is unknown. Bcl-2, an inner mitochondrial membrane protein, blocks programmed cell death in B cells. We report here that this proto-oncogene maintains immune responsiveness. Transgenic mice overproducing Bcl-2 have a long-term persistence of immunoglobulin-secreting cells and an extended lifetime for memory B cells.
Nuñez
G
G
Howard Hughes Medical Institute, Washington University School of Medicine, Saint Louis, Missouri 63110.
Hockenbery
D
D
McDonnell
T J
TJ
Sorensen
C M
CM
Korsmeyer
S J
SJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002470:Cell Survival; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013861:Thiocyanates
D000941:Antigens; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013861:Thiocyanates; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D016650:Fluorescein-5-isothiocyanate