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Nat Immunol. 2015 May;16(5):534-43. doi: 10.1038/ni.3141. Epub 2015 Apr 6.

Responsiveness of B cells is regulated by the hinge region of IgD.

Author information

1
Institute of Immunology, University Hospital Ulm, Ulm, Germany.
2
BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
3
1] Institute of Immunology, University Hospital Ulm, Ulm, Germany. [2] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
4
Department of Bioinformatics, Institute for Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
5
Department of Laboratory Medicine, Medical University of Vienna and Center for Molecular Medicine (CeMM), Austrian Academy of Sciences, Vienna, Austria.
6
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
7
1] Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Turumi-ku, Kanagawa, Japan. [2] Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
8
Chair of Genetics, Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
9
1] BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [2] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [3] Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
10
1] Institute of Immunology, University Hospital Ulm, Ulm, Germany. [2] BIOSS Center for Biological Signaling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany. [3] Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany.

Abstract

Mature B cells express immunoglobulin M (IgM)- and IgD-isotype B cell antigen receptors, but the importance of IgD for B cell function has been unclear. By using a cellular in vitro system and corresponding mouse models, we found that antigens with low valence activated IgM receptors but failed to trigger IgD signaling, whereas polyvalent antigens activated both receptor types. Investigations of the molecular mechanism showed that deletion of the IgD-specific hinge region rendered IgD responsive to monovalent antigen, whereas transferring the hinge to IgM resulted in responsiveness only to polyvalent antigen. Our data suggest that the increased IgD/IgM ratio on conventional B-2 cells is important for preferential immune responses to antigens in immune complexes, and that the increased IgM expression on B-1 cells is essential for B-1 cell homeostasis and function.

PMID:
25848865
DOI:
10.1038/ni.3141
[Indexed for MEDLINE]

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