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Control of B-cell responses by Toll-like receptors

Nature volume 438, pages 364–368 (2005)Cite this article

Abstract

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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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, 300 Cedar Street, Connecticut, 06510, New Haven, USA

    Chandrashekhar Pasare & Ruslan Medzhitov

Authors
  1. Chandrashekhar Pasare
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  2. Ruslan Medzhitov
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Corresponding author

Correspondence to Ruslan Medzhitov.

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. 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). https://doi.org/10.1038/nature04267

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