Requirement for JNK-dependent upregulation of BimL in anti-IgM-induced apoptosis in murine B lymphoma cell lines WEHI-231 and CH31.

Abstract

The cross-linking of B cell receptor (BCR) undergoes growth arrest, accompanied by apoptosis, in the CH31 and WEHI-231 B lymphoma cells, a model representing primary immature B cells. We have previously demonstrated that sustained activation of c-Jun N-terminal kinase (JNK) is required for BCR-mediated apoptosis. In the present study, we examined how the anti-IgM-induced prolonged activation of JNK results in apoptosis. Anti-IgM upregulated the expression levels of three isoforms of Bim protein, especially BimL, which appeared to be dependent on JNK activation. In contrast to protein expression, BimL mRNA levels were down-regulated upon anti-IgM stimulation, suggesting that anti-IgM-induced upregulation of BimL is regulated through post-transcriptional control. Upon JNK activation, phosphorylated form of JNK, together with Bax migrated from cytosol to mitochondria. In unstimulated cells, BimL protein was complexed with Bcl-x(L) and changed the partner to associate with Bax on the mitochondrial membrane after ligation of BCR, leading to initiation of apoptotic processes. Retroviral transduction of BimL into WEHI-231 cells overexpressing dominant-negative form of JNK1 (dnJNK1) resulted in a comparable level of apoptotic cells to control cells, whereas the BimL-mediated apoptosis was partially prevented by Bcl-x(L). Taken together, engagement of BCR with anti-IgM results in association of Bax-alpha with BimL in the mitochondria, at least in part, through a sustained activation of JNK.

• Authors: Eiko Takada, Kikumi Hata, Junichiro Mizuguchi
• Journal: Experimental cell research (Exp Cell Res) Vol. 312 Issue 19 Pg. 3728-38 (Nov 15 2006) ISSN: 0014-4827 [Print] United States
• PMID: 17007835 (Publication Type: Journal Article)

Chemical References

• Antibodies, Anti-Idiotypic
• Apoptosis Regulatory Proteins
• Bax protein, mouse
• Bcl-2-Like Protein 11
• Bcl2l1 protein, mouse
• Bcl2l11 protein, mouse
• DNA Primers
• Immunoglobulin M
• Membrane Proteins
• Protein Isoforms
• Proto-Oncogene Proteins
• Receptors, Antigen, B-Cell
• Recombinant Proteins
• bcl-2-Associated X Protein
• bcl-X Protein
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Antibodies, Anti-Idiotypic (administration & dosage)
• Apoptosis (immunology)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Base Sequence
• Bcl-2-Like Protein 11
• Biological Transport, Active
• Cell Line, Tumor
• DNA Primers (genetics)
• Immunoglobulin M
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lymphoma, B-Cell (genetics, immunology, metabolism, pathology)
• Membrane Proteins (genetics, metabolism)
• Mice
• Protein Isoforms (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Receptors, Antigen, B-Cell (metabolism)
• Recombinant Proteins (genetics, metabolism)
• Transduction, Genetic
• Up-Regulation
• bcl-2-Associated X Protein (metabolism)
• bcl-X Protein (metabolism)