Bcl10 can promote survival of antigen-stimulated B lymphocytes.
To understand the nature of negative responses through the B-cell antigen receptor (BCR), we have screened an expression cDNA library for the ability to block BCR-induced growth arrest and apoptosis in the immature B-cell line, WEHI-231. We isolated multiple copies of full-length, unmutated Bcl10, a signaling adaptor molecule encoded by a gene found to translocate to the immunoglobulin heavy chain (IgH) locus in some mucosa-associated lymphoid tissue (MALT) lymphomas. A conditionally active form of B-cell lymphoma 10 (Bcl10) protected WEHI-231 cells from BCR-induced apoptosis upon activation. Induction of Bcl10 activity caused rapid activation of nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK), but not activation of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein (MAP) kinases. These results support genetic and biochemical experiments that have implicated Bcl10 and its binding partners Carma1 and MALT1 in mediating the ability of the BCR to activate NF-kappaB. The ability of Bcl10 expression to prevent BCR-induced growth arrest and apoptosis of WEHI-231 cells was dependent on NF-kappaB activation. Finally, overexpression of Bcl10 in primary B cells activated ex vivo promoted the survival of these cells after removal of activating stimuli. Taken together these results support the hypothesis that enhanced BCL10 expression caused by translocation to the IGH locus can promote formation of MALT lymphomas.
Tian
Maoxin Tim
MT
Department of Microbiology and Immunology, UCSF, 513 Parnassus Ave, San Francisco, CA 94143-0414, USA.
Gonzalez
Gabriel
G
Scheer
Barbara
B
DeFranco
Anthony L
AL
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors; D014161:Transduction, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D048031:JNK Mitogen-Activated Protein Kinases