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Lineage Reconstruction of In Vitro Identified Antigen-Specific Autoreactive B Cells from Adaptive Immune Receptor
Peter Blazso1,2, Krisztian Csomos2, Christopher M Tipton3
1Department of Pediatrics, University of Szeged, 6720 Szeged, Hungary.
International Journal of Molecular Sciences
|January 8, 2023
Summary
We developed ImmChainTracer to analyze autoreactive B-cell lineages in autoimmune diseases like lupus. This computational tool reconstructs B-cell receptor repertoires, revealing clonal expansion and maturation in patients.
Area of Science:
- Immunology
- Computational Biology
- Genetics
Background:
- Autoreactive (AR) B-cell clones drive humoral autoimmunity, leaving traces in B-cell receptor repertoires.
- Analyzing polyreactive (PR) and AR B-cell lineages requires reconstructing their clonal relationships from adaptive immune receptor repertoire (AIRR) datasets.
Purpose of the Study:
- To develop a computational approach for reconstructing and visualizing AR and PR B-cell lineages.
- To apply this method to identify and track AR IgH sequences in patients with autoimmune diseases.
Main Methods:
- Developed ImmChainTracer, a computational tool for extracting and visualizing B-cell lineage members and clonal relationships.
- Applied ImmChainTracer to IgH repertoires from patients with RAG1/2 deficiency (pRD) and systemic lupus erythematosus (SLE).
Main Results:
- Successfully identified relatives of AR IgH sequences and tracked their fate in AIRRs.
- Observed signs of clonal expansion, affinity maturation, and class-switching in both PR/AR and non-PR/AR B-cell lineages.
- Demonstrated the utility of ImmChainTracer in studying B-cell lymphogenesis in autoimmune contexts.
Conclusions:
- ImmChainTracer enables the reconstruction and analysis of AR and PR B-cell lineages.
- The method provides insights into B-cell dynamics in autoimmune diseases.
- Potential for broader application in studying B-cell expansion triggered by various factors, including infections and vaccinations.
Keywords:
AIRRB cell lineageIgH repertoireRAG deficiencySLEautoimmunityautoreactive B cellsmonoclonal antibodyMore Related Videos
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