The interplay between T helper subset cytokines and IL-12 in directing human B lymphocyte differentiation

✍ Scribed by Alenka Gagro; John Gordon

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 183 KB
• Volume: 29
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(199910)29:10<3369::aid-immu3369>3.0.co;2-#

✦ Synopsis

This study asks how T helper (TH) subset cytokines impact upon IL-12-directed change in B cells engaged in signaling via the B cell receptor and CD40, essential components in the initiation of T-dependent B cell responses. For B cells stimulated in this way, IL-12 promoted a distinct phenotype highlighted by the hyper-expression of CD38: the Th1 cytokine IFN-+ reproduced the IL-12 effects while neutralizing antibody to IFN-+ reversed IL-12-dependent change. The divergent pathway of differentiation promoted by the Th2 cytokine IL-4 (characterized by hyper-induction of CD23) was left unchecked by IL-12. IL-10 was found to dampen IL-12 actions by suppressing IL-12-dependent IFN-+ production but failed to perturb the effects of exogenous IFN-+ . Thus, IL-12 -by invoking autocrine IFN-+ productionpromotes phenotypic deviation in B cells engaging T-dependent signals. The reversal of such Th1 driving of B cells by IL-10 only when the source of IFN-+ is endogenous and the inability of IL-12 to impact upon IL-4-directed differentiation suggest a progressive and hierarchical commitment of B cells to polarization during a developing T-dependent response dominated at the level of the Th cell rather than that of the dendritic cell.