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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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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. |
format | Online Article Text |
id | pubmed-5940257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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