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Kidins220/ARMS binds to the B cell antigen recptor and regulates B cell development and activation

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Fiala,  Gina J.
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg;
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Janowska,  Iga
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;

/persons/resource/persons191279

Prutek,  F.
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191108

Hobeika,  E.
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;
Institute of Immunology, University Hospital Ulm;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Plum,  Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;

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Reth,  Michael
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191217

Minguet,  Susanna
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Schamel,  Wolfgang W. A.
Centre for Biological Signaling Studies (BIOSS), University of Freiburg;
Centre of Chronic Immunodeficiency, (CCI), University of Freiburg;
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Fiala, G. J., Janowska, I., Prutek, F., Hobeika, E., Satapathy, A., Sprenger, A., et al. (2015). Kidins220/ARMS binds to the B cell antigen recptor and regulates B cell development and activation. The Journal of Experimental Medicine, 212(10), 1693-1708.


Cite as: https://hdl.handle.net/someHandle/test/escidoc:902501
Abstract
B cell antigen receptor (BCR) signaling is critical for B cell development and activation. Using mass spectrometry, we identified a protein kinase D-interacting substrate of 220 kD (Kidins220)/ankyrin repeat-rich membrane-spanning protein (ARMS) as a novel interaction partner of resting and stimulated BCR. Upon BCR stimulation, the interaction increases in a Src kinase-independent manner. By knocking down Kidins220 in a B cell line and generating a conditional B cell-specific Kidins220 knockout (B-KO) mouse strain, we show that Kidins220 couples the BCR to PLCγ2, Ca(2+), and extracellular signal-regulated kinase (Erk) signaling. Consequently, BCR-mediated B cell activation was reduced in vitro and in vivo upon Kidins220 deletion. Furthermore, B cell development was impaired at stages where pre-BCR or BCR signaling is required. Most strikingly, λ light chain-positive B cells were reduced sixfold in the B-KO mice, genetically placing Kidins220 in the PLCγ2 pathway. Thus, our data indicate that Kidins220 positively regulates pre-BCR and BCR functioning.