SARS-CoV-2 infection relaxes peripheral B cell tolerance

Area of Science:

• Immunology
• Virology
• Pathogenesis of Infectious Diseases

Background:

• Severe SARS-CoV-2 infection triggers significant inflammation and autoantibody production.
• B cell Newfoundland (BND) cells are a subset of autoreactive, anergic B lymphocytes.
• Inflammatory stimuli can potentially overcome peripheral B cell tolerance in BND cells.

Purpose of the Study:

• To investigate if SARS-CoV-2-associated inflammation impairs peripheral tolerance in BND cells.
• To determine the impact of SARS-CoV-2 infection on BND cell phenotype and function.

Main Methods:

• Collected peripheral blood mononuclear cells (PBMCs) and plasma from healthy controls, SARS-CoV-2-vaccinated individuals, and patients with convalescent or severe SARS-CoV-2 infection.
• Analyzed BND cell activation, inhibitory receptor expression, and B cell receptor (BCR) signaling.
• Assessed levels of autoreactive antibodies.

Main Results:

• BND cells from severely infected individuals showed significant activation, reduced inhibitory receptor expression, and restored BCR signaling.
• These alterations indicate a breach in BND cell anergy during severe SARS-CoV-2 infection.
• Phenotypic and functional BND cell changes correlated with increased systemic inflammation.

Conclusions:

• Autoreactive BND cells are released from peripheral tolerance during severe SARS-CoV-2 infection.
• This loss of tolerance is likely driven by robust systemic inflammation associated with the infection.
• Understanding this mechanism may offer insights into the autoimmune complications of severe COVID-19.