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

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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.