Involvement of NAK-1, the human nur77 homologue, in surface IgM-mediated apoptosis in Burkitt lymphoma cell line BL41.

The induction of apoptosis via surface IgM (sIgM) in immature B cells requires de novo transcription. To investigate the regulation of activation-induced cell death (AICD) in B cells we used a cell line model consisting of an Epstein-Barr virus-negative Burkitt lymphoma cell line (BL41), which is highly sensitive, and a subclone which is resistant to sIgM-mediated apoptosis (BL41/B5). Resistance in this cell line was not due to down-regulation of sIgM or functional impairment in signal transduction of the surface Ig complex. The zinc finger transcription factor nur77 has been implicated to play an important role in CD3-mediated apoptosis in murine T cells. We were able to demonstrate that surface IgM ligation and subsequent apoptosis in BL41 cells is associated with a concomitant induction of NAK-1, the human nur77 homologue. Induction of NAK-1 mRNA and DNA binding activity in the nucleus could be readily observed by means of Northern blot and electrophoretic mobility shift assay, respectively. In contrast, the resistant clone BL41/B5 did not show any NAK-1 expression upon stimulation. This suggests a role for NAK-1 in sIgM-mediated apoptosis of immature B cells.