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.
【초록키워드】 antibodies, SARS-CoV-2, Inflammation, Tolerance, viral infection, SARS-COV-2 infection, Infection, Anergy, B cell, PBMC, plasma, systemic inflammation, convalescent, expression, BCR, Signaling, Evidence, autoantibody, B lymphocytes, subject, infected individual, alteration, individual, healthy controls, phenotypic, inhibitory receptor, inflammatory stimuli, Cell, self-antigens, severe SARS-CoV-2, immunized, peripheral tolerance, robust, collected, significantly, reduced, supported, functional, activated, restored, subset, released, impair, in healthy individual, asked, 【제목키워드】 Tolerance, SARS-COV-2 infection, B cell,