The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

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Item Type:	Article
Title:	The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity
Creators Name:	Salzer, E., Zoghi, S., Kiss, M.G., Kage, F., Rashkova, C., Stahnke, S., Haimel, M., Platzer, R., Caldera, M., Ardy, R.C., Hoeger, B., Block, J., Medgyesi, D., Sin, C., Shahkarami, S., Kain, R., Ziaee, V., Hammerl, P., Bock, C., Menche, J., Dupré, L., Huppa, J.B., Sixt, M., Lomakin, A., Rottner, K., Binder, C.J., Stradal, T.E.B., Rezaei, N. and Boztug, K.
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.
Keywords:	Autoimmune Diseases, Autoimmunity, B-Lymphocytes, Bone Marrow Transplantation, Cell Line, Cytoskeleton, Infant, Membrane Proteins, Inbred C57BL Mice, Knockout Mice, T-Lymphocytes
Source:	Science Immunology
ISSN:	2470-9468
Publisher:	American Association for the Advancement of Science
Volume:	5
Number:	49
Page Range:	eabc3979
Date:	10 July 2020
Official Publication:	https://doi.org/10.1126/sciimmunol.abc3979
PubMed:	View item in PubMed

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