Production of hematopoietic growth factors by human b lymphocytes: Mechanisms and possible implications

Abstract

In this study we have investigated the ability of human B lymphocytes to produce granulocyte-macrophage colony stimulating factor (GM-CSF) and, in preliminary experiments, granulocyte CSF (G-CSF). The sources of human B cells were surgically removed tonsils from normal individuals and peripheral blood from patients with B cell chronic lymphocytic leukemia (B-CLL). Tonsil B lymphocytes were purified by E rosetting and complement-mediated cytotoxicity with selected monoclonal antibodies and subsequently fractionated by a Percoll density gradient into in vivo activated and resting cells. The latter cell fractions were subsequently cultured with or without stimuli. GM-CSF was detected by a bioassay, G-CSF by an enzyme-linked immunoassay. In vivo and in vitro activated B cells produced GM-CSF, whereas in vivo activated, but not in vitro activated, B lymphocytes produced G-CSF. These results were confirmed by Northern blot experiments with cDNA probes specific for GM-CSF and G-CSF genes. Many B cell suspensions from B-CLL patients produced GM-CSF or G-CSF only following Staphylococcus Aureus Cowan I (SAC) stimulation; in some cases, a spontaneous production or no production at all of the two cytokines was detected. The possible implications of these results for B cell physiology and for the pathogenesis of immunologically mediated diseases will be discussed.

Granulocyte colony‐stimulating factor production by adult T‐cell leukaemia cells

“…Although we had no direct evidence, the tumour cells of the remaining three cases were also suspected of producing G‐CSF. In contrast to normal B lymphocytes and natural killer cells that produce G‐CSF (Cuturi et al , 1989; Pistoia et al , 1994), normal T‐lymphocytes are not thought to produce this cytokine (Oster et al , 1989). Further, there has been only one reported case of G‐CSF‐producing malignant T‐cell lymphoma to date (Ohtsuki et al , 1992).…”

The Role of Neutrophils in the Pathogenesis of Chronic Lymphocytic Leukemia

“…In line with these reports, the depletion of G-CSF and GM-CSF in CLL-conditional medium reduces the survival capacity of neutrophils [ 33 ]. Both G-CSF and GM-CSF are produced by CLL cells [ 59 ]. On the other hand it is worth mentioning that the effect of GM-CSF is pleiotropic and this cytokine is also used as a therapy.…”

Optimized retroviral transduction of mouse T cells for in vivo assessment of gene function

“…To test this idea and circumvent this potential problem, we devised a simple strategy to separate these two T-cell populations. Previously activated human lymphocytes have been separated by density centrifugation because of their lower overall density 20,21 . Thus, we tested whether Percoll density centrifugation could also enrich the larger-sized ‘blasting’ T cells on day 1 after in vitro stimulation (Fig.…”