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MHC class II expression is differentially regulated in plasmacytoid and conventional dendritic cells

Nature Immunology volume 5, pages 899–908 (2004)Cite this article

Abstract

Major histocompatibility complex (MHC) class II–restricted antigen presentation is essential for the function of dendritic cells (DCs). We show here that plasmacytoid DCs (pDCs) differ from all other DC subsets with respect to expression of CIITA, the 'master regulator' of MHC class II genes. The gene encoding CIITA is controlled by three cell type–specific promoters: pI, pIII and pIV. With gene targeting in mice, we demonstrate that pDCs rely strictly on the B cell promoter pIII, whereas macrophages and all other DCs depend on pI. The molecular mechanisms driving MHC class II expression in pDCs are thus akin to those operating in lymphoid rather than myeloid cells.

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Figure 1: Generation of p(III+IV)-deficient mice.
Figure 2: Mice deficient in p(III+IV) lack MHC class II expression on all B cells.
Figure 3: B cells depend on pIII for driving CIITA and MHC class II expression.
Figure 4: The promoter pI is sufficient for driving MHC class II expression in macrophages.
Figure 5: The promoter pI is sufficient for driving CIITA and MHC class II expression in DCs.
Figure 6: DCs from p(III+IV)-deficient mice remain functional IFN-γ.
Figure 7: The pDCs depend on pIII for driving CIITA and MHC class II expression.
Figure 8: CIITA expression is not silenced during the maturation of pDCs.

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Acknowledgements

We thank N. Mach for the Flt3L-secreting B16 melanoma cell line; D. Wohlwend for assistance with cell sorting; P. Douillard for help with the immunofluorescence of epidermal sheets; C. Asselin-Paturel for suggestions on the in vitro generation of pDCs; and G. Biollaz and A. Fontana for the isolation and analysis of microglia and astrocytes. Supported by the Roche Research Foundation and the Ernst and Lucie Schmidheiny Foundation (S.L.-L.), the Swiss National Science Foundation, the Swiss Multiple Sclerosis Society and the National Center of Competence and Research on Neural Plasticity and Repair.

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Author notes

  1. Jean-Marc Waldburger

    Present address: Division of Rheumatology, University Hospital, 1211, Geneva, Switzerland

  2. Salomé LeibundGut-Landmann and Jean-Marc Waldburger: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Immunology, University of Geneva Medical School, Geneva, 1211, Switzerland

    Salomé LeibundGut-Landmann, Jean-Marc Waldburger & Walter Reith

  2. Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, WC2A 3PX, UK

    Caetano Reis e Sousa

  3. Department of Biochemistry, Faculty of Biology and Medicine, University of Lausanne, Epalinges, 1066, Switzerland

    Hans Acha-Orbea

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  1. Salomé LeibundGut-Landmann
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Supplementary information

Supplementary Fig. 1

The loss of pIV results in the absence of MHC class II expression on cells of non-hematopoietic origin. (PDF 99 kb)

Supplementary Fig. 2

Antibody production in response to a T cell-independent antigen is normal in p(III+IV) deficient mice. (PDF 39 kb)

Supplementary Fig. 3

Impact of the deletion of pIII and pIV on the kinetics of IFN-g induced CIITA and MHC class II expression in macrophages. (PDF 61 kb)

Supplementary Fig. 4

Negative selection by endogenous mtv superantigen is conserved in p(III+IV) deficient mice. (PDF 38 kb)

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LeibundGut-Landmann, S., Waldburger, JM., e Sousa, C. et al. MHC class II expression is differentially regulated in plasmacytoid and conventional dendritic cells. Nat Immunol 5, 899–908 (2004). https://doi.org/10.1038/ni1109

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