Reciprocal regulatory effects of IL-4 on cell growth and immunoglobulin production in Ig-secreting human B-cell lines.
The effects of interleukin-4 (IL-4) on cell proliferation and immunoglobulin (Ig) production from three different Ig-secreting B-cell lines (U266, IgE; HSCE-, IgG; LA 350, IgM) were analyzed. Addition of IL-4 increased Ig production by the IgE- and IgG-secreting cell lines and this was paralleled by an inhibition of cellular proliferation. In contrast, the addition of IL-4 to LA 350 cells stimulated cellular proliferation but a decrease in IgM secretion. With each cell line, the IL-4 effects were both dose- and time-dependent and effects were maximal in the presence of 400 U/ml. Further analysis of the mechanism of IL-4 action on Ig production at the single B-cell level using an ELISA spot assay revealed a dualistic effect: increased Ig levels in culture supernatants reflected both an enhancement of single-cell Ig production as well as an increase in numbers of Ig-secreting B cells (IgE and IgG). In LA 350 cells the number of IgM-secreting B cells was suppressed as well as the amount of Ig released by single cells. These data on Ig production were supported by determination of mRNA amounts for the epsilon, gamma, and mu gene transcripts. Addition of IL-4 enhanced the levels of epsilon and gamma message in U266 and HSCE- cells, respectively, and reduced the amount of mu mRNA in LA 350 cells. In the IgE- and IgG-secreting cell lines, the IL-4 effect also correlated with enhanced expression of IL-4 receptor (IL-4R) mRNA levels, whereas IL-4R mRNA levels were unchanged in IgM-producing cells after IL-4 treatment. Incubation of cells with IL-4 and interferon-gamma abolished the stimulatory activities of IL-4 on either cell proliferation (LA 350 cells) or Ig production (HSCE- and U266); but did not influence the inhibitory activities of IL-4 on the cell lines. The immunosuppressive drug cyclosporin A (CsA) inhibited both cell proliferation and Ig production in all three cell lines to a similar degree. Furthermore, in U266 and HSCE- cells, CsA inhibition could not be overcome by IL-4. These data support the conclusion that on Ig-secreting human B-cell lines, IL-4 regulates cell proliferation and Ig production in a reciprocal fashion.
Renz
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H
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Or
R
R
Domenico
J
J
Leung
D Y
DY
Gelfand
E W
EW
D000921:Antibody-Producing Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics
D007136:Immunoglobulins; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine