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 1-3. Even so, a secondary immune response can be generated years after a primary exposure to antigen 4. Antigen that might restimulate B cells persists for extended periods on follicular dendritic cells in the light zone of germinal centres 5-13. Antigen binding B cells have also been found months after the end of obvious cell division 14. The precise signal that enables certain B cells to emerge as long-term surviving memory cells 14-17 is unknown. Bcl-2, an inner mitochondrial membrane protein 18, blocks programmed cell death in B cells 18-20. 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.