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Control of B-cell responses by Toll-like receptors


Toll-like receptors (TLRs) detect microbial infection and have an essential role in the induction of immune responses1,2,3. TLRs can directly induce innate host defence responses, but the mechanisms of TLR-mediated control of adaptive immunity are not fully understood. Although TLR-induced dendritic cell maturation is required for activation of T-helper (TH) cells4, the role of TLRs in B-cell activation and antibody production in vivo is not yet known. Here we show that activation and differentiation of TH cells is not sufficient for the induction of T-dependent B-cell responses. We find that, in addition to CD4+ T-cell help, generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells.

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Figure 1: T-cell activation is insufficient to induce normal antibody responses.
Figure 2: Defective antibody production by MyD88 knockout B cells is B-cell intrinsic.
Figure 3: Differential requirements for TLR activation on B cells by T-dependent and T-independent antigens.
Figure 4: TLR signalling influences several aspects of B-cell activation and differentiation.
Figure 5: Activation of dendritic cells and T cells is insufficient to induce normal antibody responses in a MyD88 complementation model.


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This research was supported by a grant from the NIH. R.M. is an investigator of the Howard Hughes Medical Institute. We thank L. Kopp for providing flagellin, N. Palm for help with analysing the CD11c-MyD88 transgenic mice, and S. Akira for providing MyD88- and TLR4-deficient mice.

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Correspondence to Ruslan Medzhitov.

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Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Figure Legends

Legends for Supplementary Figures 1–6. (DOC 35 kb)

Supplementary Figure 1

Lower levels of total immunoglobulin isotypes in sera of MyD88KO mice. (PDF 46 kb)

Supplementary Figure 2

Naive B cells from WT and MyD88KO mice have comparable phenotypes. (PDF 70 kb)

Supplementary Figure 3

Comparable secretion of cytokines by activated T cells in µMT mice. (PDF 17 kb)

Supplementary Figure 4

B cells express TLR5. (PDF 52 kb)

Supplementary Figure 5

Defective germinal centre reaction by cells deficient in TLR signalling. (PDF 3488 kb)

Supplementary Figure 6

Analysis of MyD88-deficient mice expressing MyD88 under the control of CD11c promoter. (PDF 194 kb)

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Pasare, C., Medzhitov, R. Control of B-cell responses by Toll-like receptors. Nature 438, 364–368 (2005).

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