title: The A-Myb transcription factor is a marker of centroblasts in vivo.
abstract: The A-Myb transcription factor is structurally related to the c-myb proto-oncogene and is involved in the control of proliferation and/or differentiation of mature B lymphocytes. We have shown previously by PCR analysis that A-myb is preferentially expressed in CD38+ CD39- sIgM- mature B cells. We demonstrate here, using in situ hybridization, that A-myb expression is restricted to the dark zone of human tonsils and lymph nodes. Furthermore, we show that A-Myb expression is cell cycle regulated both in tonsillar B cells and in Burkitt's lymphoma cell lines, being detectable only in the S and G2/M phases of the cell cycle and not in G0/G1 phase. Strong proliferation of resting human B cells induced in vitro by a variety of physiologic signals, including anti-mu, CD40 ligand, IL-2, IL-4, IL-6, IL-13, IFN-gamma, TNF-alpha, anti-CD19, and anti-CD20, failed to induce A-myb expression, suggesting that proliferation alone is not sufficient for A-myb expression in the absence of induction of a true centroblast phenotype. Finally, we show that differentiation of germinal center B cells in vitro toward either memory or plasma cells is accompanied by rapid down-regulation of A-myb expression. We conclude that A-myb is a marker of centroblasts generated in vivo.
authors.affiliation: Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Golay
authors.forename: V
authors.initials: V
authors.lastname: Broccoli
authors.forename: G
authors.initials: G
authors.lastname: Lamorte
authors.forename: C
authors.initials: C
authors.lastname: Bifulco
authors.forename: C
authors.initials: C
authors.lastname: Parravicini
authors.forename: A
authors.initials: A
authors.lastname: Pizzey
authors.forename: N S
authors.initials: NS
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Delia
authors.forename: P
authors.initials: P
authors.lastname: Ferrauti
authors.forename: D
authors.initials: D
authors.lastname: Vitolo
authors.forename: M
authors.initials: M
authors.lastname: Introna
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D015415:Biomarkers; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015415:Biomarkers; C000715470:MAS1 protein, human; C088831:MYBL1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators