Endogenous secretion of IL-4 maintains growth and Thy-1 expression of a transformed B cell clone.
The CD5+ B cell lymphoma clone, CH12.LX, endogenously produces IL-4. Blocking the binding of this IL-4 to its cellular receptor inhibited the continuous proliferation of CH12.LX. mAb specific for either IL-4 or the IL-4R profoundly and specifically inhibited the proliferation of CH12.LX cells in a concentration-dependent manner, within 4 h after the addition of mAb. The addition of exogenous rIL-4 alone to CH12.LX cells had no effect on either proliferation or antibody secretion. However, exogenous rIL-4 was able to counteract the effects of anti-IL-4 antibody. Treatment of CH12.LX cells with antisense RNA oligodeoxynucleotides to IL-4 also specifically inhibited cell proliferation and decreased the levels of IL-4 secreted into the culture supernatants by more than 50%, without effect on total RNA or protein synthesis. Effects of antisense IL-4 were also blocked by addition of exogenous IL-4. Control oligodeoxynucleotides of equal size and base composition had no effect, and IL-4 antisense oligodeoxynucleotides did not effect the growth of a B cell lymphoma clone which does not produce IL-4. Blocking the binding of endogenously produced IL-4 to CH12.LX cells did not change the levels of membrane IL-4R or CD5 molecules. However, the constitutive expression of Thy-1 by these B cells was markedly decreased, and anti-Thy-1 antibodies decreased proliferation and PMA-induced aggregation of CH12.LX cells. Autocrine secretion of IL-4 thus appears to be required both for the continuous proliferation of CH12.LX B cells, as well as their expression of Thy-1, which may function either as a homotypic adhesion molecule or a signal transduction molecule for these cells. These findings indicate that endogenously produced lymphokines may play a critical role in the maintenance of B cell hyperproliferative disorders.
Louie
S W
SW
Department of Microbiology, University of Iowa, Iowa City 52242.
Ramirez
L M
LM
Krieg
A M
AM
Maliszewski
C R
CR
Bishop
G A
GA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002449:Cell Aggregation; D002455:Cell Division; D002999:Clone Cells; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D018800:Thy-1 Antigens; D015847:Interleukin-4; D007371:Interferon-gamma