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. 1998 Apr;93(4):498–504. doi: 10.1046/j.1365-2567.1998.00460.x

Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine immunoglobulin-secreting B-cell hybridomas.

T Iwasaki 1, T Hamano 1, J Fujimoto 1, E Kakishita 1
PMCID: PMC1364127  PMID: 9659221

Abstract

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.

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Selected References

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