LAMTOR2 (p14) controls B cell differentiation by orchestrating endosomal BCR trafficking

  • B-cell development and function depend on stage-specific signaling through the B-cell antigen receptor (BCR). Signaling and intracellular trafficking of the BCR are connected, but the molecular mechanisms of this link are incompletely understood. Here, we investigated the role of the endosomal adaptor protein and member of the LAMTOR/Ragulator complex LAMTOR2 (p14) in B-cell development. Efficient conditional deletion of LAMTOR2 at the pre-B1 stage using mb1-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using Cd19-Cre mice permitted analysis of residual B cells at later developmental stages, revealing that LAMTOR2 was critical for the generation and activation of mature B lymphocytes. Loss of LAMTOR2 resulted in aberrant BCR signaling due to delayed receptor internalization and endosomal trafficking. In conclusion, we identify LAMTOR2 as critical regulator of BCR trafficking and signaling that is essential for early B-cell development in mice.

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Author:Marcin Łyszkiewicz, Daniel Kotlarz, Natalia Karolina Zie̜tara, Gudrun Brandes, Jana Diestelhorst, Silke Glage, Elias Hobeika, Michael Reth, Lukas A. Huber, Andreas Krueger, Christoph Klein
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Thomas L. Rothstein
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/03/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/16
Tag:B cells; B-cell antigen receptor; LAMTOR2; p14; signal transduction; trafficking
Issue:Art. 497
Page Number:11
First Page:1
Last Page:11
Copyright © 2019 Łyszkiewicz, Kotlarz, Ziȩtara, Brandes, Diestelhorst, Glage, Hobeika, Reth, Huber, Krueger and Klein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0