Journal of Clinical Immunology

, Volume 35, Issue 3, pp 254–263 | Cite as

A mutation in the human tetraspanin CD81 gene is expressed as a truncated protein but does not enable CD19 maturation and cell surface expression

  • Felipe Vences-Catalán
  • Chiung-Chi Kuo
  • Yael Sagi
  • Homer Chen
  • Neta Kela-Madar
  • Menno C. van Zelm
  • Jacques J. M. van Dongen
  • Shoshana Levy
Original Research


A homozygous mutation in a splice site of the CD81 gene was identified previously in a patient, as the cause in a case of common variable immune deficiency (CVID). CD19 expression is reduced in mice that lack CD81; however, B cells in this patient lacked completely CD19 surface expression. The mutation led to an absence of the CD81 protein on the cell surface and it was assumed that the CD81 protein was not produced. Here we demonstrate that a truncated human CD81 mutant (CD81mut) was actually produced, but retained intracellularly. We also demonstrate that the truncated CD81mut protein is in close proximity to the intracellularly sequestered CD19. However, this interaction does not enable normal CD19 maturation and surface expression. In addition, we show that specific domains of CD81 enable retrieval and trafficking of human CD19 to the cell surface. Finally, we demonstrate that surface expression of CD19 requires CD81, even in non-B cells.


Protein trafficking ER glycosylation B cells 



We thank Dr. Ronald Levy for critically editing the manuscript, Dr. Laurence Cocquerel for the hepatocyte Huh-7 CD81POS and Huh-7w7 CD81NEG cell lines, Debra Czerwinski for help with flow cytometric analyses and Dr. Francisco Sanchez Madrid for CD81shRNA.

Disclosure of conflict of interest

None of the authors have a conflict of interest.

Authorship contribution

FVC and CCK contributed equally to this work. FVC, CCK, YS, HC and NKM designed, performed and collected data, MCvZ and JMvD EBV-transformed and generated the patient’s B cell line, SL, FVC and YS designed the research, analyzed the data and wrote the manuscript.

Supported by a Specialized Center of Research (SCOR) grant from the Leukemia and Lymphoma Society.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Felipe Vences-Catalán
    • 1
  • Chiung-Chi Kuo
    • 1
  • Yael Sagi
    • 1
  • Homer Chen
    • 1
  • Neta Kela-Madar
    • 1
  • Menno C. van Zelm
    • 2
  • Jacques J. M. van Dongen
    • 2
  • Shoshana Levy
    • 1
  1. 1.Department of Medicine, Division of OncologyStanford University Medical CenterStanfordUSA
  2. 2.Department of Immunology, Erasmus MCUniversity Medical CenterRotterdamNetherlands

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