TY  - JOUR
A1  - Łyszkiewicz, Marcin
A1  - Kotlarz, Daniel
A1  - Zie̜tara, Natalia Karolina
A1  - Brandes, Gudrun
A1  - Diestelhorst, Jana
A1  - Glage, Silke
A1  - Hobeika, Elias
A1  - Reth, Michael
A1  - Huber, Lukas A.
A1  - Krueger, Andreas
A1  - Klein, Christoph
T1  - LAMTOR2 (p14) controls B cell differentiation by orchestrating endosomal BCR trafficking
T2  - Frontiers in immunology
N2  - 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.
KW  - B cells
KW  - B-cell antigen receptor
KW  - LAMTOR2
KW  - signal transduction
KW  - trafficking
KW  - p14
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50024
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-500244
SN  - 1664-3224
N1  - 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.
VL  - 10
IS  - Art. 497
SP  - 1
EP  - 11
PB  - Frontiers Media
CY  - Lausanne
ER  -