AUTHOR=Łyszkiewicz Marcin , Kotlarz Daniel , Ziȩtara Natalia , Brandes Gudrun , Diestelhorst Jana , Glage Silke , Hobeika Elias , Reth Michael , Huber Lukas A. , Krueger Andreas , Klein Christoph 

TITLE=LAMTOR2 (p14) Controls B Cell Differentiation by Orchestrating Endosomal BCR Trafficking

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00497

DOI=10.3389/fimmu.2019.00497

ISSN=1664-3224

ABSTRACT=<p>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 <italic>mb1</italic>-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using <italic>Cd19</italic>-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.</p>