B cell receptor-mediated apoptosis of human lymphocytes is associated with a new regulatory pathway of Bim isoform expression.
Studies in Bim-deficient mice have shown that the proapoptotic molecule Bim plays a key role in the control of B cell homeostasis and activation. However, the role of Bim in human B lymphocyte apoptosis is unknown. We show in this study that, depending on the degree of cross-linking, B cell receptors can mediate both Bim-dependent and apparent Bim-independent apoptotic pathways. Cross-linked anti-mu Ab-mediated activation induces an original pathway governing the expression of the various Bim isoforms. This new pathway involves the following three sequential steps: 1) extracellular signal-regulated kinase-dependent phosphorylation of the BimEL isoform, which is produced in large amounts in healthy B cells; 2) proteasome-mediated degradation of phosphorylated BimEL; and 3) increased expression of the shorter apoptotic isoforms BimL and BimS.
Mouhamad
Shahul
S
Institut National de la Santé et de la Recherche Médicale Unité 542, Villejuif, France.
Besnault
Laurence
L
Auffredou
Marie Thérèse
MT
Leprince
Corinne
C
Bourgeade
Marie Françoise
MF
Leca
Gérald
G
Vazquez
Aimé
A
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013347:Subcellular Fractions / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex