Golay J, Broccoli V, Lamorte G, Bifulco C, Parravicini C, Pizzey A, Thomas N S, Delia D, Ferrauti P, Vitolo D, Introna M
Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Immunol. 1998 Mar 15;160(6):2786-93.
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.
A-Myb转录因子在结构上与c-myb原癌基因相关，参与成熟B淋巴细胞增殖和/或分化的调控。我们先前通过PCR分析表明，A-myb在CD38+ CD39- sIgM-成熟B细胞中优先表达。我们在此使用原位杂交证明，A-myb的表达局限于人类扁桃体和淋巴结的暗区。此外，我们表明，A-Myb的表达在扁桃体B细胞和伯基特淋巴瘤细胞系中均受细胞周期调控，仅在细胞周期的S期和G2/M期可检测到，而在G0/G1期未检测到。多种生理信号（包括抗μ、CD40配体、IL-2、IL-4、IL-6、IL-13、IFN-γ、TNF-α、抗CD19和抗CD20）在体外诱导静止的人类B细胞强烈增殖，但未能诱导A-myb表达，这表明在未诱导真正的中心母细胞表型的情况下，仅增殖不足以诱导A-myb表达。最后，我们表明生发中心B细胞在体外向记忆细胞或浆细胞的分化伴随着A-myb表达的快速下调。我们得出结论，A-myb是体内产生的中心母细胞的标志物。
