Reversal of Blimp-1-mediated apoptosis by A1, a member of the Bcl-2 family

Blimp-1 (B lymphocyte-induced maturation protein 1) is strongly expressed d uring the late stages of B cell differentiation to immunoglobulin-secreting plasma cells. Overexpression of Blimp-1 in B lymphoma cells has been repor ted to induce either growth arrest and cell death or Ig secretion and termi nal differentiation, depending on the developmental stage of the recipient lymphomas. By using a retroviral expression system we show that Blimp-1-tra nsduced immature WEHI 231 murine B lymphoma cells produce J chain, increase d levels of the secretory form of mu heavy chain mRNA and secrete IgM for a short period of time. Concomitantly, they exhibit altered ratios of c-myc/ mad4 mRNA levels, a reduction in the expression of the anti-apoptotic bcl-2 family member A1 and a distinct growth disadvantage, followed by cell deat h. Reintroduction of A1 by retroviral transduction greatly extends the life span of Blimp-1-expressing WEHI 231 cells which continue to secrete IgM. T hese data suggest that levels of A1 may determine the checkpoint between de ath and survival of Blimp-1-expressing B cells at different stages of diffe rentiation.