The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity

The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity Publisher Pubmed

Salzer E^{1, 2, 3, 4} ; Zoghi S^{1, 2, 3, 5, 6} ; Kiss MG^{3, 7} ; Kage F^{8, 9} ; Rashkova C^{1, 3, 10} ; Stahnke S⁹ ; Haimel M^{1, 2, 3} ; Platzer R¹¹ ; Caldera M³ ; Ardy RC^{1, 2, 3} ; Hoeger B^{1, 2, 3} ; Block J^{1, 2, 3} ; Medgyesi D¹ ; Sin C³ Show All Authors

Salzer E^{1, 2, 3, 4}
Zoghi S^{1, 2, 3, 5, 6}
Kiss MG^{3, 7}
Kage F^{8, 9}
Rashkova C^{1, 3, 10}
Stahnke S⁹
Haimel M^{1, 2, 3}
Platzer R¹¹
Caldera M³
Ardy RC^{1, 2, 3}
Hoeger B^{1, 2, 3}
Block J^{1, 2, 3}
Medgyesi D¹
Sin C³
Shahkarami S^{5, 12, 13}
Kain R¹⁴
Ziaee V^{15, 16}
Hammerl P¹⁷
Bock C^{1, 3}
Menche J³
Dupre L^{1, 18}
Huppa JB¹¹
Sixt M¹⁹
Lomakin A^{1, 2, 3}
Rottner K^{8, 9}
Binder CJ^{3, 7}
Stradal TEB⁹
Rezaei N^{5, 6, 20}
Boztug K^{1, 2, 3, 4}

Show Affiliations

1. Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria
2. St. Anna Childrenâ€™s Cancer Research Institute (CCRI), Vienna, Austria
3. CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
4. St. Anna Childrenâ€™s Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
5. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
6. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
8. Division of Molecular Cell Biology, Zoological Institute, Technische Universitat Braunschweig, Braunschweig, Germany
9. De-partment of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
10. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
11. Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
12. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
13. Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran
14. De-partment of Pathology, Medical University of Vienna, Vienna, Austria
15. Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
16. Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
17. Department of Molecular Biology, University of Salzburg, Salzburg, Austria
18. Center for Pathophysiology of Toulouse Purpan, INSERM UMR1043, CNRS UMR5282, Paul Sabatier University, Toulouse, France
19. Institute of Science and Technology Austria, Klosterneuburg, Austria
20. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

Source: Science Immunology Published:2020

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

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Style	Citing Format
MLA	Salzer E, et al.. "The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity." Science Immunology, vol. 5, no. 49, 2020, pp. -.
APA	Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, Haimel M, Platzer R, Caldera M, Ardy RC, Hoeger B, Block J, Medgyesi D, Sin C, Shahkarami S, Kain R, Ziaee V, Hammerl P, Bock C, ... Boztug K (2020). The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity. Science Immunology, 5(49), -.
Chicago	Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, Haimel M, et al.. "The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity." Science Immunology 5, no. 49 (2020): -.
Harvard	Salzer E et al. (2020) 'The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity', Science Immunology, 5(49), pp. -.
Vancouver	Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, et al.. The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity. Science Immunology. 2020;5(49):-.
BibTex	@article{ author = {Salzer E and Zoghi S and Kiss MG and Kage F and Rashkova C and Stahnke S and Haimel M and Platzer R and Caldera M and Ardy RC and Hoeger B and Block J and Medgyesi D and Sin C and Shahkarami S and Kain R and Ziaee V and Hammerl P and Bock C and Menche J and Dupre L and Huppa JB and Sixt M and Lomakin A and Rottner K and Binder CJ and Stradal TEB and Rezaei N and Boztug K}, title = {The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity}, journal = {Science Immunology}, volume = {5}, number = {49}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Salzer E AU - Zoghi S AU - Kiss MG AU - Kage F AU - Rashkova C AU - Stahnke S AU - Haimel M AU - Platzer R AU - Caldera M AU - Ardy RC AU - Hoeger B AU - Block J AU - Medgyesi D AU - Sin C AU - Shahkarami S AU - Kain R AU - Ziaee V AU - Hammerl P AU - Bock C AU - Menche J AU - Dupre L AU - Huppa JB AU - Sixt M AU - Lomakin A AU - Rottner K AU - Binder CJ AU - Stradal TEB AU - Rezaei N AU - Boztug K TI - The Cytoskeletal Regulator Hem1 Governs B Cell Development and Prevents Autoimmunity JO - Science Immunology VL - 5 IS - 49 SP - EP - PY - 2020 ER -

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