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

Abstract
Data availability
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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

(2020) Crystal structure of human CD81 large extracellular loop in complex with 5A6 Fab
Protein Data Bank, 6U9S.

https://www.rcsb.org/structure/6U9S

Article and author information

Author details

Katherine J Susa

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
No competing interests declared.
Tom CM Seegar

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
No competing interests declared.
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..
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..

"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.

Copyright

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.