Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells.
In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Carlsson
M
M
Department of Pathology, University Hospital, Uppsala, Sweden.
Tötterman
T H
TH
Rosén
A
A
Nilsson
K
K
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D007378:Interleukins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D004247:DNA