Autoantibodies elicited with SARS-CoV-2 infection are linked to alterations in double negative B cells.

Autor:	Castleman MJ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States., Stumpf MM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States., Therrien NR; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States., Smith MJ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.; Barbara Davis Center for Diabetes, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, United States., Lesteberg KE; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.; Department of Medicine, Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, United States., Palmer BE; Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, United States., Maloney JP; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, United States., Janssen WJ; Department of Medicine, National Jewish Health, Denver, CO, United States.; Department of Medicine, University of Colorado, Aurora, CO, United States., Mould KJ; Department of Medicine, National Jewish Health, Denver, CO, United States.; Department of Medicine, University of Colorado, Aurora, CO, United States., Beckham JD; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.; Department of Medicine, Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, United States.; Rocky Mountain Regional Veterans affairs (VA), Medical Center, Aurora, CO, United States., Pelanda R; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States., Torres RM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 05; Vol. 13, pp. 988125. Date of Electronic Publication: 2022 Sep 05 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.988125
Abstrakt:	Double negative (DN) B cells (CD27-IgD-) comprise a heterogenous population of DN1, DN2, and the recently described DN3 and DN4 subsets. In autoimmune disease, DN2 cells are reported to be precursors to autoreactive antibody secreting cells and expansion of DN2 cells is linked to elevated interferon levels. Severe SARS-CoV-2 infection is characterized by elevated systemic levels of pro-inflammatory cytokines and serum autoantibodies and expansion of the DN2 subset in severe SARS-CoV-2 infection has been reported. However, the activation status, functional capacity and contribution to virally-induced autoantibody production by DN subsets is not established. Here, we validate the finding that severe SARS-CoV-2 infection is associated with a reduction in the frequency of DN1 cells coinciding with an increase in the frequency of DN2 and DN3 cells. We further demonstrate that with severe viral infection DN subsets are at a heightened level of activation, display changes in immunoglobulin class isotype frequency and have functional BCR signaling. Increases in overall systemic inflammation (CRP), as well as specific pro-inflammatory cytokines (TNFα, IL-6, IFNγ, IL-1β), significantly correlate with the skewing of DN1, DN2 and DN3 subsets during severe SARS-CoV-2 infection. Importantly, the reduction in DN1 cell frequency and expansion of the DN3 population during severe infection significantly correlates with increased levels of serum autoantibodies. Thus, systemic inflammation during SARS-CoV-2 infection drives changes in Double Negative subset frequency, likely impacting their contribution to generation of autoreactive antibodies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Castleman, Stumpf, Therrien, Smith, Lesteberg, Palmer, Maloney, Janssen, Mould, Beckham, Pelanda and Torres.)
Databáze:	MEDLINE
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