Key points are not available for this paper at this time.
CD40 mAb at subsaturating doses inhibit the growth of transformants of the M12 murine cell line expressing intact full length CD40 molecules (M12/CD40+ cells) but do not inhibit the growth of two M12 transformants expressing either a mutant CD40 cDNA missing most of the cytoplasmic tail (CD40/tailless) or a mutant cDNA with a substitution at residue 234 (CD40/234A, Ala for Thr). Using these transformants, we tested a panel of cytokines for the ability to mimic CD40 mAb. rIL-6 behaved like CD40 mAb and inhibited the growth of M12/CD40+ cells but not of CD40/tailless or CD40/234A mutants. The effect of IL-6 on M12/CD40+ cells not only required intact CD40 including threonine 234 but also was specific because IL-6 mAb blocked the inhibitory activity. The M12/CD40+ cells responsive to IL-6 expressed greater than 300,000 CD40 molecules/cells but, like M12/CD40-controls, expressed only small numbers (less than 50/cell) of high affinity IL-6R, indicating that CD40 is not a receptor for IL-6. Nevertheless, IL-6 utilizes intact CD40 efficiently when it signals these cells: treatment of M12/CD40+ cells with IL-6 induced increased phosphorylation of CD40. Conversely, triggering CD40 on M12/CD40+ cells leads to IL-6 production. Similar effects were evident in human CD40+ B cells: IL-6 increased the phosphorylation of CD40 in the IL-6-responsive cell line, CESS, and CD40 mAb induced IL-6 production in activated human B cells. Thus, CD40 may function to receive and regulate IL-6-dependent signals in B cells.
Clark et al. (Sat,) studied this question.