ARID3a-Expressing Naïve B Cells in SLE have an Activated Phenotype and Transiently Express Surface CD68

Area of Science:

• Immunology
• Molecular Biology
• Autoimmunity Research

Background:

• Increased numbers of AT-Rich Interaction Domain 3a (ARID3a)-expressing B lymphocytes correlate with heightened disease activity in systemic lupus erythematosus (SLE).
• Normally rare, ARID3a-expressing circulating naïve B cells significantly increase their expression in SLE patients.
• Activated naïve B cells and double-negative B cells (IgD- CD27-) in healthy individuals can be induced to express ARID3a in vitro.

Purpose of the Study:

• To investigate the role of ARID3a in B cell activation and its association with autoimmunity in SLE.
• To identify novel markers of autoreactive B cell precursors in SLE.
• To explore the relationship between ARID3a expression and B cell activation markers.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of naïve B cells from SLE patients.
• In vitro stimulation of B lymphocytes from healthy donors with cytokines and agonists.
• Flow cytometry and gene expression analysis to assess ARID3a and CD68 co-expression.
• Functional assays to evaluate the effect of ARID3a inhibition on B cell activation.

Main Results:

• scRNA-seq revealed that ARID3a-associated genes in SLE B cells included activation markers.
• Unexpected co-expression of scavenger receptor CD68 with ARID3a was observed at both transcript and protein levels in activated naïve B cells.
• Inhibition of ARID3a in stimulated B cell cultures suppressed naïve B cell activation and CD68 expression.

Conclusions:

• ARID3a is implicated in the activation of naïve B cells and the development of autoimmunity in SLE.
• CD68 is identified as a novel co-marker with ARID3a in autoreactive B cell precursors.
• ARID3a and CD68 represent potential biomarkers for identifying B cell subsets associated with SLE pathogenesis.