Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21^low B cells in hepatitis C virus-cured mixed cryoglobulinemia.

ABSTRACT:

Introduction

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses.

Methods

Clonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differen

SUBMITTER: Del Padre M 

PROVIDER: S-EPMC9945227 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature