title: The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers.
abstract: Germinal centers (GCs) are sites of intense B cell proliferation and are central for T cell-dependent antibody responses. However, the role of c-Myc, a key cell-cycle regulator, in this process has been questioned. Here we identified c-Myc(+) B cell subpopulations in immature and mature GCs and found, by genetic ablation of Myc, that they had indispensable roles in the formation and maintenance of GCs. The identification of these functionally critical cellular subsets has implications for human B cell lymphomagenesis, which originates mostly from GC B cells and frequently involves MYC chromosomal translocations. As these translocations are generally dependent on transcription of the recombining partner loci, the c-Myc(+) GC subpopulations may be at a particularly high risk for malignant transformation.
authors.affiliation: Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, USA. dinis.calado@mdc-berlin.de
authors.forename: Dinis Pedro
authors.initials: DP
authors.lastname: Calado
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Susana A
authors.initials: SA
authors.lastname: Godinho
authors.forename: Alex
authors.initials: A
authors.lastname: Pellerin
authors.forename: Karl
authors.initials: K
authors.lastname: Köchert
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sleckman
authors.forename: Ignacio Moreno
authors.initials: IM
authors.lastname: de Alborán
authors.forename: Martin
authors.initials: M
authors.lastname: Janz
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D017930:Genes, Reporter; D056426:Genetic Loci; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049452:Green Fluorescent Proteins; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D049452:Green Fluorescent Proteins