1. Academic Validation
  2. Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency

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

  • J Exp Med. 2018 May 7;215(5):1327-1336. doi: 10.1084/jem.20170534.
Baerbel Keller 1 Moneef Shoukier 2 Kathrin Schulz 3 Arshiya Bhatt 3 Ines Heine 3 Valentina Strohmeier 1 Carsten Speckmann 2 Niklas Engels 3 Klaus Warnatz 1 Jürgen Wienands 4
Affiliations

Affiliations

  • 1 Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 2 Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
  • 3 Institute of Cellular & Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.
  • 4 Institute of Cellular & Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany jwienan@uni-goettingen.de.
Abstract

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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