Role of the interleukin 2 receptor in differentiation of a clone of Ly-1+ B cells.
CH12.LX, an in vitro subclone of a murine B cell lymphoma that makes IgM reactive with sheep erythrocytes (SRBC), has cell surface receptors for the lymphokine interleukin 2 (IL 2). The binding of recombinant murine IL 2 to these receptors did not stimulate CH12.LX cells to differentiate and secrete antibody. However, the binding of either of two monoclonal antibodies (Mab) specific for the IL 2 receptor increased the proportion of CH12.LX cells that secrete hemolytic IgM. The effect did not require the presence of antigen. One of the Mab, 3C7, is known to block the binding of IL2 to its receptor on T cells, whereas the other, 7D4, which also reacts with the IL 2 receptor, does not block the binding of IL 2. The differentiation of CH12.LX induced by 3C7, but not that induced by 7D4, was inhibited by recombinant IL 2. Neither IL 2 (up to 200 U/ml) nor 3C7 (up to 10 micrograms/ml) had any significant influence on incorporation of [3H]thymidine; 7D4 at 10 micrograms/ml decreased thymidine incorporation by about 60%. Mitomycin C and hydroxyurea, which both inhibit the incorporation of [3H]thymidine into CH12.LX cells, also both induce antibody secretion. In both cases, the concentration necessary to cause differentiation is substantially lower than that needed to cause detectable inhibition of thymidine uptake. We conclude that the IL 2 receptor on CH12.LX cells is a functional signal transducing molecule, and we discuss the possible inverse relationship between proliferation and differentiation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000950:Antigens, Ly / Q000032:analysis*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology; D004261:DNA Replication / Q000187:drug effects; D007075:Immunoglobulin M / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000502:physiology*; D008223:Lymphoma; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D007075:Immunoglobulin M; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins