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Updated: Jul 15, 2026

Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Identification and characterization of bone marrow plasma cells producing IFN-γ-neutralizing autoantibodies in
Han Wang1, Qianqian Yang1, Tian Zhao2
1Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing 100084, China.
Abstract:
Adult-onset immunodeficiency (AOID) can be associated with anti-interferon (IFN)-γ autoantibodies (AIGAs). Rituximab (RTX) reduces circulating B cells but often fails to eliminate AIGAs, suggesting the presence of long-lived antibody-secreting cells (ASCs) in immune-privileged sites. Here, we identified 23 distinct IFN-γ-specific monoclonal antibodies (mAbs) from bone marrow (BM) ASCs of AOID patients using microwell array chip technology and single-cell RNA sequencing. Competitive assays demonstrated that neutralizing mAbs disrupt IFN-γ engagement with IFN-γR1 or IFN-γR2, impairing JAK-STAT1 signaling. Structural analysis of neutralizing mAb A01BM-03 revealed its binding to a quaternary epitope on dimeric IFN-γ, disrupting IFN-γR2 interaction. Notably, clonally expanded IFN-γ-specific ASCs were localized within a CD11c+ZEB2+ age-associated B cell (ABC)-like plasma cell cluster in one AOID patient, implicating its role in AOID pathogenesis. These findings provide direct evidence for IFN-γ-specific ASCs in the BM despite RTX treatment, supporting targeted ASC therapy to restore immune homeostasis in AOID.
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