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  Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance

Minguet, S., Kläsener, K., Schaffer, A.-M., Fiala, G. J., Osteso-Ibánez, T., Raute, K., et al. (2017). Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance. Nature Immunology, 18, 1150-1159. doi:10.1038/ni.3813.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-8579-A Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-857A-8
Genre: Journal Article

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 Creators:
Minguet, Susana1, 2, 3, 4, Author
Kläsener, Kathrin1, 2, 5, Author
Schaffer, Anna-Maria1, 3, Author
Fiala, Gina J1, 2, Author
Osteso-Ibánez, Teresa4, Author
Raute, Katrin1, 2, 6, Author
Navarro-Lérida, Inmaculada4, Author
Hartl, Frederike A1, 2, Author
Seidl, Maximilian3, 7, Author
Reth, Michael1, 2, 5, Author
Pozo, Miguel A Del4, Author
Affiliations:
1Department of Immunology, University of Freiburg, Freiburg, Germany, ou_persistent22              
2Centre for Biological Signalling Studies BIOSS, University of Freiburg, Freiburg, Germany, ou_persistent22              
3Center for Chronic Immunodeficiency (CCI), University of Freiburg, Freiburg, Germany, ou_persistent22              
4Mechanoadaptation & Caveolae Biology Lab. Centro Nacional de Investigaciones Cardiovasculares Carlos (CNIC), Madrid, Spain, ou_persistent22              
5Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
6Spemann Graduate School for Biology, University of Freiburg, Freiburg, Germany, ou_persistent22              
7Institute for Surgical Pathology, University of Freiburg, Freiburg, Germany, ou_persistent22              

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 Abstract: Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo. In immature Cav1-deficient B cells, altered nanoscale organization of IgM-BCRs resulted in a failure of receptor editing and a skewed repertoire of B cells expressing immunoglobulin-μ heavy chains with hallmarks of poly- and auto-reactivity, which ultimately led to autoimmunity in mice. Thus, Cav1 emerges as a cell-intrinsic regulator that prevents B cell-induced autoimmunity by means of its role in plasma-membrane organization.

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Language(s): eng - English
 Dates: 2017-10
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ni.3813
 Degree: -

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Title: Nature Immunology
  Other : Nat. Immunol.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 18 Sequence Number: - Start / End Page: 1150 - 1159 Identifier: ISSN: 1529-2908
CoNE: https://pure.mpg.de/cone/journals/resource/974392607073