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Wagner, M.* ; Poeck, H.* ; Jahrsdoerfer, B.* ; Rothenfusser, S.* ; Prell, D.* ; Bohle, B.* ; Tuma, E.* ; Giese, Th.* ; Ellwart, J.W. ; Endres, S.* ; Hartmann, G.*

IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA.

J. Immunol. 172, 954-963 (2004)

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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The detection of microbial molecules via Toll-like receptors (TLR) in B cells is not well characterized. In this study, we found that both naive and memory B cells lack TLR4 (receptor for LPS) but express TLR9 (receptor for CpG motifs) and produce IL-6, TNF-{alpha}, and IL-10 upon stimulation with CpG oligonucleotides (ODN), synthetic mimics of microbial DNA. Consistent with the lack of TLR4, purified B cells failed to respond to LPS. Similar to CpG ODN, CD40 ligand (CD40L) alone induced IL-6, TNF-{alpha}, and IL-10. Production of these cytokines as well as IgM synthesis was synergistically increased when both CpG ODN and CD40L were combined. Unlike IL-6, TNF-{alpha}, and IL-10, the Th1 cytokine IL-12p70 was detected only when both CpG ODN and CD40L were present, and its induction was independent of B cell receptor cross-linking. CpG ODN did not increase the capacity of CD40L-activated B cells to induce proliferation of naive T cells. However, B cells activated with CpG ODN and CD40L strongly enhanced IFN-{gamma} production in developing CD4 T cells via IL-12. Together, these results demonstrate that IL-12p70 production in human B cells is under the dual control of microbial stimulation and T cell help. Our findings provide a molecular basis for the potent adjuvant activity of CpG ODN to support humoral immune responses observed in vivo, and for the limited value of LPS.

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