Complement C4A Regulates Autoreactive B Cells in Murine Lupus.

Autor:	Simoni L; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA., Presumey J; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA., van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA., Castrillon C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA., Chang SE; Department of Medicine, Division of Immunology, and Institute for Immunity Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA., Utz PJ; Department of Medicine, Division of Immunology, and Institute for Immunity Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.carroll@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Nov 03; Vol. 33 (5), pp. 108330.
DOI:	10.1016/j.celrep.2020.108330
Abstrakt:	Systemic lupus erythematosus (SLE) is a severe autoimmune disease mediated by pathogenic autoantibodies. While complement protein C4 is associated with SLE, its isoforms (C4A and C4B) are not equal in their impact. Despite being 99% homologous, genetic studies identified C4A as more protective than C4B. By generating gene-edited mouse strains expressing either human C4A or C4B and crossing these with the 564lgi lupus strain, we show that, overall, C4A-like 564Igi mice develop less humoral autoimmunity than C4B-like 564Igi mice. This includes a decrease in the number of GCs, autoreactive B cells, autoantibodies, and memory B cells. The higher efficiency of C4A in inducing self-antigen clearance is associated with the follicular exclusion of autoreactive B cells. These results explain how the C4A isoform is protective in lupus and suggest C4A as a possible replacement therapy in lupus. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu