Complement C4A Regulates Autoreactive B Cells in Murine Lupus.

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. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Léa Simoni, Jessy Presumey, Cees E van der Poel, Carlos Castrillon, Sarah E Chang, Paul J Utz, Michael C Carroll. Complement C4A Regulates Autoreactive B Cells in Murine Lupus. Cell reports. 2020 Nov 03;33(5):108330

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PMID: 33147456

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