Corcione A, Pistoia V
Laboratory of Oncology, Scientific Institute G. Gaslini, Genoa, Italy.
Methods. 1997 Jan;11(1):143-7. doi: 10.1006/meth.1996.0398.
Biologically active granulocyte-colony stimulating factor (G-CSF) was released spontaneously in culture by in vivo activated tonsillar B lymphocytes and, in particular, by the germinal center (GC) B-cell subset. In contrast, mantle zone B cells failed to produce the cytokine under any of the culture conditions tested. A CD40 monoclonal antibody (mAb), recombinant (r) IL4, and the combination of the CD40 mAb and rIL4 all increased G-CSF production by GC B cells. The augmentation of G-CSF release correlated with the increased survival of GC B cells. rG-CSF rescued GC B cells from apoptosis, suggesting that the cytokine may be utilized in autocrine and/or paracrine ways. Neoplastic B cells from follicular center cell lymphoma patients, which are the counterparts of normal GC B lymphocytes, also released G-CSF spontaneously in culture. In contrast, malignant B cells from a subset of chronic lymphocytic leukemia (CLL) patients had to be stimulated with Staphylococcus aureus Cowan I or CD40 mAb in combination with rIL4 or rIL2 to produce G-CSF in vitro. Some B-CLL cell suspensions were rescued from spontaneous apoptosis following culture in the presence of rG-CSF. Taken together, these studies provide the first demonstration that G-CSF (i) is produced by either normal or neoplastic human B lymphocytes and (ii) participates in the modulation of apoptosis of the same cells.
生物活性粒细胞集落刺激因子（G-CSF）在体内激活的扁桃体B淋巴细胞培养物中自发释放，尤其是生发中心（GC）B细胞亚群。相比之下，套区B细胞在任何测试的培养条件下均未能产生细胞因子。一种CD40单克隆抗体（mAb）、重组（r）IL4以及CD40 mAb与rIL4的组合均增加了GC B细胞的G-CSF产生。G-CSF释放的增加与GC B细胞存活率的提高相关。rG-CSF使GC B细胞免于凋亡，提示该细胞因子可能以自分泌和/或旁分泌方式发挥作用。滤泡中心细胞淋巴瘤患者的肿瘤性B细胞是正常GC B淋巴细胞的对应物，在培养中也自发释放G-CSF。相比之下，一部分慢性淋巴细胞白血病（CLL）患者的恶性B细胞必须用金黄色葡萄球菌Cowan I或CD40 mAb与rIL4或rIL2联合刺激才能在体外产生G-CSF。在rG-CSF存在的情况下培养后，一些B-CLL细胞悬液从自发凋亡中被挽救。综上所述，这些研究首次证明G-CSF（i）由正常或肿瘤性人类B淋巴细胞产生，（ii）参与调节相同细胞的凋亡。
