IMMUNOLOGY2025™ Conference Recordings-B cell isoform usage alterations in systemic lupus erythematosus

B cell isoform usage alterations in systemic lupus erythematosus

Video Transcription

Video Summary

The talk described a study on differential isoform usage in B cells from systemic lupus erythematosus (SLE) patients. The speaker explained that most lupus risk variants are non-coding, making their function unclear, and proposed that many may affect alternative splicing rather than only gene expression. By analyzing published RNA-seq data from multiple B-cell subsets, the team found widespread dysregulation of splicing factors and hundreds of genes with altered isoform usage, especially in double-negative (DN2) B cells.  <br /><br />IRF5, a key interferon-related transcription factor, showed a strong splicing signal and was prioritized for follow-up. CRISPR deletion of IRF5 in primary B cells reduced DN2 proliferation, activation markers, and production of IL-6 and IL-12. The group also found dynamic IRF5 promoter/isoform usage during differentiation, and showed that an SLE risk variant near the IRF5 promoter increased IRF5 expression and shifted promoter usage. The study suggests lupus risk variants can alter B-cell splicing and IRF5 regulation.

Keywords

systemic lupus erythematosus

B cells

alternative splicing

IRF5

isoform usage