SARS-CoV-2 infection relaxes peripheral B cell tolerance.
J Exp Med
; 219(6)2022 06 06.
Article
in English
| MEDLINE | ID: covidwho-1788448
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peripheral Tolerance
/
COVID-19
Limits:
Humans
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Jem.20212553
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