Production of hematopoietic growth factors by human B lymphocytes: mechanisms and possible implications.
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.
Pistoia
V
V
Laboratory of Immunopathology, Scientific Institute Giannina Gaslini, Genoa, Italy.
Corcione
A
A
Baldi
L
L
Zupo
S
S
Dono
M
M
Ferrarini
M
M
D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D015973:Gene Expression Regulation, Leukemic; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor