Zurück zur Übersicht
| Science immunology. pii: 5/49/eabc3979. doi: 10.1126/sciimmunol.abc3979 |
| The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity. |
| Salzer E1, Zoghi S2, Kiss MG3, Kage F4, Rashkova C5, Stahnke S6, Haimel M7, Platzer R8, Caldera M9, Ardy RC10, Hoeger B11, Block J12, Medgyesi D13, Sin C14, Shahkarami S15, Kain R16, Ziaee V17, Hammerl P18, Bock C19, Menche J20, Dupré L21, Huppa JB22, Sixt M23, Lomakin A24, Rottner K25, Binder CJ26, Stradal TEB27, Rezaei N28, Boztug K29 |
 Author information
|
|
Abstract The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1 mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity. |
|
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
|
Publikations ID: 32646852 Quelle: öffnen |
Author information
Schnellinfo
-- Cancer Care
-- Kliniken und Partner
-- CCC Cancer School
-- Young CCC
-- CCC Tumorboards
-- CCC Forschungscluster
-- CCC Units
-- CCC Platforms
-- SOPs / Leitlinien
-- Kontakt
Featured
