title: Differential c-Myc responsiveness to B cell receptor ligation in B cell-negative selection.
abstract: Responsiveness of c-Myc oncogene to B cell receptor ligation has been implicated in the induction of apoptosis in transformed and normal immature B cells. These studies provided compelling evidence to link the c-Myc oncogene with the process of negative selection in B-lymphocytes. However, in addition to apoptosis, B cell-negative selection has been shown to occur by secondary Ig gene rearrangements, a mechanism called receptor editing. In this study, we assessed whether differential c-Myc responsiveness to B cell receptor (BCR) ligation is associated with the mechanism of negative selection in immature B cells. Using an in vitro bone marrow culture system and an Ig-transgenic mouse model (3-83) we show here that c-Myc is expressed at low levels throughout B cell development and that c-Myc responsiveness to BCR ligation is developmentally regulated and increased with maturation. Furthermore, we found that the competence to mount c-Myc responsiveness upon BCR ligation is important for the induction of apoptosis and had no effect on the process of receptor editing. Therefore, this study suggests an important role of c-Myc in promoting and/or maintaining B cell development and that compartmentalization of B cell tolerance may also be developmentally regulated by differential c-Myc responsiveness.
authors.affiliation: Department of Immunology, Technion Faculty of Medicine, Haifa 31096, Israel.
authors.forename: Nira
authors.initials: N
authors.lastname: Leider
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000276:immunology*; D016259:Genes, myc / Q000276:immunology*; D008024:Ligands; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D017393:RNA Editing / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000235:genetics
chemical_list: D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D008024:Ligands; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2