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.
Mapara
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Humboldt University, Virchow Klinikum, Robert Rössle Klinik, Department of Internal Medicine (Medical Oncology and Tumorimmunology) Berlin-Buch, Germany.
Weinmann
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P
Bommert
K
K
Daniel
P T
PT
Bargou
R
R
Dörken
B
B
D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000494:pharmacology; D008969:Molecular Sequence Data; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors