Bcl-2 maintains B cell memory

Abstract

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.

Resistance of T-cells to apoptosis in autoimmune diabetic (NOD) mice is increased early in life and is associated with dysregulated expression of Bcl-x

“…In mice bearing the ipr mutation, elimination of specific T-cell clones following in vivo neonatal injection of a superantigen is incomplete and of short duration [25]. Finally, in mice bearing a Bcl-2 transgene, the antibody response following antigen stimulation is prolonged [26]. These observations indicate that apoptosis is associated with the sedation of an autoimmune response and, conversely, that resistance to apoptosis causes prolongation of an immune response or delays clonal downsizing.…”

Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation

“…Overall, these results confirm and extend previous observations showing that the expression of bcl-2 largely varies in normal individuals along the B-cell differentiation, the amount of this protein per cell correlating with the expected cellular lifespan. 27,32,33 Especially interesting is the observation that during the rearrangement of the immunoglobulin genes in BM B-cell precursors, bcl-2 expression is extremely low probably reflecting that at this stage, B-cell precursors are particularly prone to apoptosis that would facilitate the prevention of survival of nonfunctional B cells.…”

t(14;18), a journey to eternity

“…Bcl-2 overexpression in the B cell lineage prolongs antibody responses upon antigenic challenge, 69 and prolongs B cell memory. 70 After a relatively long latency period, 11% of these mice develop monoclonal high-grade diffuse large cell immunoblastic lymphoma. 60 This clearly demonstrates that t(14;18)s may occasionally occur in every individual, but these cells disappear over time or are specifically eliminated by the immune system.…”