SARS-CoV-2 infection relaxes peripheral B cell tolerance
| Autor: | Moriah J. Castleman, Megan M. Stumpf, Nicholas R. Therrien, Mia J. Smith, Kelsey E. Lesteberg, Brent E. Palmer, James P. Maloney, William J. Janssen, Kara J. Mould, J. David Beckham, Roberta Pelanda, Raul M. Torres |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Experimental Medicine. 219 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20212553 |
| Popis: | Severe SARS-CoV-2 infection is associated with strong inflammation and autoantibody production against diverse self-antigens, suggesting a system-wide defect in B cell tolerance. BND cells are a B cell subset in healthy individuals harboring autoreactive but anergic B lymphocytes. In vitro evidence suggests inflammatory stimuli can breach peripheral B cell tolerance in this subset. We asked whether SARS-CoV-2–associated inflammation impairs BND cell peripheral tolerance. To address this, PBMCs and plasma were collected from healthy controls, individuals immunized against SARS-CoV-2, or subjects with convalescent or severe SARS-CoV-2 infection. We demonstrate that BND cells from severely infected individuals are significantly activated, display reduced inhibitory receptor expression, and restored BCR signaling, indicative of a breach in anergy during viral infection, supported by increased levels of autoreactive antibodies. The phenotypic and functional BND cell alterations significantly correlate with increased inflammation in severe SARS-CoV-2 infection. Thus, autoreactive BND cells are released from peripheral tolerance with SARS-CoV-2 infection, likely as a consequence of robust systemic inflammation. |
| Databáze: | OpenAIRE |
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