title: The proto-oncogene c-myc regulates antibody secretion and Ig class switch recombination.
abstract: The immune response involves the generation of Ab-secreting cells and memory B cells through a process called terminal B lymphocyte differentiation. This program requires the transcriptional repressor Blimp-1, which inhibits c-myc expression and terminates proliferation. Although the role of c-Myc in cell proliferation is well characterized, it is not known whether it has other functions in terminal differentiation. In this study, we show that c-Myc not only regulates cell proliferation, but it is also essential for Ab-secreting cell function and differentiation in vivo. c-Myc-deficient B lymphocytes hypersecrete IgM and do not undergo Ig class switch recombination (CSR). CSR has been previously linked to proliferation, and in this study we mechanistically link class switching and proliferation via c-Myc. We observed that c-Myc regulates CSR by transcriptionally activating the B cell-specific factor activation-induced cytidine deaminase. By linking cell proliferation and CSR, c-Myc is thus a critical component for a potent immune response.
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Madrid E-28049, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Fernández
authors.forename: Maitane
authors.initials: M
authors.lastname: Ortiz
authors.forename: Lorena
authors.initials: L
authors.lastname: Rodríguez
authors.forename: Arancha
authors.initials: A
authors.lastname: García
authors.forename: Dolores
authors.initials: D
authors.lastname: Martinez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moreno de Alborán
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology* / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase