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.
Corcione
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Laboratory of Oncology, Scientific Institute G. Gaslini, Genoa, Italy.
Pistoia
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D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4