EXPRESSION OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR GENES IN PARTIALLY OVERLAPPING MONOCLONAL B-CELL POPULATIONS FROM CHRONIC LYMPHOCYTIC-LEUKEMIA PATIENTS

B lymphocytes were purified from the peripheral blood of 30 B-cell chr onic lymphocytic leukemia (B-CLL) patients and tested for the ability to produce granulocyte colony-stimulating factor (G-CSF) in vitro. Fif teen Staphylococcus aureus Cowan I (SAC)-stimulated, but not unstimula ted, B-cell suspensions produced G-CSF in short-term cultures. Accordi ngly, G-CSF mRNA was detected only in SAC-stimulated B cells, Five CLL B-cell fractions that released G-CSF following exposure to SAC were a lso incubated with CD40 or anti-mu antibodies in the presence or absen ce of recombinant (r) interleukin-2 (IL-2) or IL-4. The 5 cell suspens ions produced G-CSF only on culture with GD40 monoclonal antibody in c ombination with rIL-2 or rIL-4. CD5+ B lymphocytes, which represent th e normal counterparts of most B-CLL proliferations, did not produce G- CSF under any of the above culture conditions. G-CSF produced by leuke mic B lymphocytes was biologically active, because conditioned media o f SAC-stimulated cells supported the in vitro growth of myeloid coloni es from normal bone marrow progenitors. The colony stimulating activit y of CLL B-cell supernatants was ascribed to both G-CSF and granulocyt e-macrophage colony stimulating factor, G-CSF receptors (G-CSFRs) were detected on freshly isolated B lymphocytes from 7 of 11 B-CLL patient s; 5 of these cell suspensions produced G-CSF in culture, whereas 2 di d not, rG-CSF rescued 3 of the 7 G-CSFR(+) cell fractions from spontan eous apoptosis but had no effect on their in vitro proliferation. (C) 1996 by The American Society of Hematology.