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Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency

Ubiquitously expressed Cbl-interacting protein of 85 kD (CIN85) is a multifunctional adapter molecule supposed to regulate numerous cellular processes that are critical for housekeeping as well as cell type–specific functions. However, limited information exists about the in vivo roles of CIN85, bec...

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Autores principales: Keller, Baerbel, Shoukier, Moneef, Schulz, Kathrin, Bhatt, Arshiya, Heine, Ines, Strohmeier, Valentina, Speckmann, Carsten, Engels, Niklas, Warnatz, Klaus, Wienands, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940257/
https://www.ncbi.nlm.nih.gov/pubmed/29636373
http://dx.doi.org/10.1084/jem.20170534
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author Keller, Baerbel
Shoukier, Moneef
Schulz, Kathrin
Bhatt, Arshiya
Heine, Ines
Strohmeier, Valentina
Speckmann, Carsten
Engels, Niklas
Warnatz, Klaus
Wienands, Jürgen
author_facet Keller, Baerbel
Shoukier, Moneef
Schulz, Kathrin
Bhatt, Arshiya
Heine, Ines
Strohmeier, Valentina
Speckmann, Carsten
Engels, Niklas
Warnatz, Klaus
Wienands, Jürgen
author_sort Keller, Baerbel
collection PubMed
description Ubiquitously expressed Cbl-interacting protein of 85 kD (CIN85) is a multifunctional adapter molecule supposed to regulate numerous cellular processes that are critical for housekeeping as well as cell type–specific functions. However, limited information exists about the in vivo roles of CIN85, because only conditional mouse mutants with cell type–specific ablation of distinct CIN85 isoforms in brain and B lymphocytes have been generated so far. No information is available about the roles of CIN85 in humans. Here, we report on primary antibody deficiency in patients harboring a germline deletion within the CIN85 gene on the X chromosome. In the absence of CIN85, all immune cell compartments developed normally, but B lymphocytes showed intrinsic defects in distinct effector pathways of the B cell antigen receptor, most notably NF-κB activation and up-regulation of CD86 expression on the cell surface. These results reveal nonredundant functions of CIN85 for humoral immune responses.
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spelling pubmed-59402572018-11-07 Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency Keller, Baerbel Shoukier, Moneef Schulz, Kathrin Bhatt, Arshiya Heine, Ines Strohmeier, Valentina Speckmann, Carsten Engels, Niklas Warnatz, Klaus Wienands, Jürgen J Exp Med Research Articles Ubiquitously expressed Cbl-interacting protein of 85 kD (CIN85) is a multifunctional adapter molecule supposed to regulate numerous cellular processes that are critical for housekeeping as well as cell type–specific functions. However, limited information exists about the in vivo roles of CIN85, because only conditional mouse mutants with cell type–specific ablation of distinct CIN85 isoforms in brain and B lymphocytes have been generated so far. No information is available about the roles of CIN85 in humans. Here, we report on primary antibody deficiency in patients harboring a germline deletion within the CIN85 gene on the X chromosome. In the absence of CIN85, all immune cell compartments developed normally, but B lymphocytes showed intrinsic defects in distinct effector pathways of the B cell antigen receptor, most notably NF-κB activation and up-regulation of CD86 expression on the cell surface. These results reveal nonredundant functions of CIN85 for humoral immune responses. Rockefeller University Press 2018-05-07 /pmc/articles/PMC5940257/ /pubmed/29636373 http://dx.doi.org/10.1084/jem.20170534 Text en © 2018 Keller et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Keller, Baerbel
Shoukier, Moneef
Schulz, Kathrin
Bhatt, Arshiya
Heine, Ines
Strohmeier, Valentina
Speckmann, Carsten
Engels, Niklas
Warnatz, Klaus
Wienands, Jürgen
Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title_full Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title_fullStr Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title_full_unstemmed Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title_short Germline deletion of CIN85 in humans with X chromosome–linked antibody deficiency
title_sort germline deletion of cin85 in humans with x chromosome–linked antibody deficiency
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940257/
https://www.ncbi.nlm.nih.gov/pubmed/29636373
http://dx.doi.org/10.1084/jem.20170534
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