Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine immunoglobulin-secreting B-cell hybridomas.
We have examined the contribution of endogenous interleukin-6 (IL-6) to the differentiation of murine B-cell hybridomas. AT73 was established by somatic hybridization between BALB/c mice B cells and 2.52M, a hypoxanthine-aminopterine-thymidine (HAT) medium-sensitive B-cell line mutant. It spontaneously secreted IgM, and addition of exogenous IL-6 augmented IgM secretion. Triggering of CD40 led to an augmentation of IL-6 expression and IgM secretion. Blocking the binding of IL-6 to its cellular receptor through the use of inhibitory monoclonal antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine role of IL-6 for the differentiation of a CD40-activated B-cell hybridoma. Co-triggering with CD40 and B-cell receptor or activation through CD40 and IL-4 led to a synergistic augmentation of IL-6 expression as well as additive IgM secretion; this was followed by a marked decrease in the expression of B-cell surface markers on the cell membrane. Furthermore, under conditions where IL-6 expression was augmented, gp80 expression was down-regulated, suggesting a negative feedback mechanism in this B-cell hybridoma. These findings provide a role by which T-cell-dependent activation through CD40 regulates an IL-6 autocrine loop, controlling B-cell differentiation.
Iwasaki
T
T
Second Department of Internal Medicine, Hyogo College of Medicine, Japan.
Hamano
T
T
Fujimoto
J
J
Kakishita
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005786:Gene Expression Regulation; D006825:Hybridomas / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007075:Immunoglobulin M; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D015847:Interleukin-4