A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking

  1. Katherine J Susa
  2. Tom CM Seegar
  3. Stephen C Blacklow  Is a corresponding author
  4. Andrew C Kruse  Is a corresponding author
  1. Harvard Medical School, United States
  2. Harvard, United States

Abstract

CD81 and its binding partner CD19 are core subunits of the B cell co-receptor complex. While CD19 belongs to the extensively studied Ig superfamily, CD81 belongs to a poorly understood family of four-pass transmembrane proteins called tetraspanins. Tetraspanins play important physiological roles by controlling protein trafficking and other processes. Here, we show that CD81 relies on its ectodomain to traffic CD19 to the cell surface. Moreover, the anti-CD81 antibody 5A6, which binds selectively to activated B cells, recognizes a conformational epitope on CD81 that is masked when CD81 is bound to CD19. Mutations of CD81 in this interface suppress its CD19 export activity. These data indicate that the CD81 - CD19 interaction is dynamically regulated upon B cell activation and this dynamism can be exploited to regulate B cell function. These results are not only valuable for understanding B cell biology, but also have important implications for understanding tetraspanin function generally.

Data availability

Diffraction data and refined coordinates have been deposited in the Protein Data Bank under accession code 6U9S.

The following data sets were generated

Article and author information

Author details

  1. Katherine J Susa

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  2. Tom CM Seegar

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  3. Stephen C Blacklow

    Department of Biological Chemistry and Molecular Pharmacology, Harvard, Boston, United States
    For correspondence
    stephen_blacklow@hms.harvard.edu
    Competing interests
    Stephen C Blacklow, S.C.B. receives funding for an unrelated project from Novartis, and is a consultant for IFM and Ayala Pharmaceuticals for unrelated projects..
  4. Andrew C Kruse

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    Andrew_Kruse@hms.harvard.edu
    Competing interests
    Andrew C Kruse, A.C.K. is a consultant on unrelated projects for the Institute for Protein Innovation, a non-profit research institute..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1467-1222

Funding

National Institutes of Health (R35 CA220340)

  • Stephen C Blacklow

National Institutes of Health (F31 HL147459)

  • Katherine J Susa

National Institutes of Health (DP5 OD02134)

  • Andrew C Kruse

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: A leuko-reduction collar was obtained from the Brigham and Women's Hospital Crimson Core with patient information de-identified. All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were reviewed and approved as exempt by the Harvard Faculty of Medicine Institutional Review Board.

Reviewing Editor

  1. Marion Pepper, University of Washington, United States

Version history

  1. Received: September 30, 2019
  2. Accepted: April 26, 2020
  3. Accepted Manuscript published: April 27, 2020 (version 1)
  4. Version of Record published: May 15, 2020 (version 2)

Copyright

© 2020, Susa et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Katherine J Susa
  2. Tom CM Seegar
  3. Stephen C Blacklow
  4. Andrew C Kruse
(2020)
A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking
eLife 9:e52337.
https://doi.org/10.7554/eLife.52337

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