B-cell-derived granulocyte-colony stimulating factor (G-CSF).

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.