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Related Experiment Video

Updated: Mar 7, 2026

The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
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Single-Cell Level Characterization of B Cell Depletion and Repopulation Following Rituximab in Systemic Lupus

Haerin Jang1, Norzawani Buang2, Catherine Sutherland1

  • 1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.

Arthritis & Rheumatology (Hoboken, N.J.)
|March 6, 2026
PubMed
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Rituximab treatment for systemic lupus erythematosus (SLE) depletes B cells, but immune cell dynamics during repopulation vary. Responders show distinct T cell changes, offering insights into treatment response.

Area of Science:

  • Immunology
  • Rheumatology
  • Genomics

Background:

  • Rituximab targets CD20+ B cells for treating systemic lupus erythematosus (SLE).
  • Patient responses to rituximab vary, necessitating a deeper understanding of B cell dynamics.
  • Immune cell shifts during B cell depletion and repopulation are not fully understood.

Purpose of the Study:

  • To longitudinally profile immune cell dynamics at single-cell resolution in SLE patients treated with rituximab.
  • To compare immune cell profiles of rituximab-treated SLE patients with healthy controls.
  • To identify differences in immune cell responses between rituximab responders and non-responders.

Main Methods:

  • Longitudinal single-cell RNA, surface protein, BCR, and TCR sequencing of 169,513 immune cells from nine SLE patients and eight healthy controls.

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  • Bulk BCR repertoire sequencing.
  • Analysis of immune cell populations, B cell receptor diversity, and gene expression changes post-rituximab treatment.

    • Main Results:

    • Rituximab induced early depletion of B cell subsets (naïve, memory, ABCs), followed by transitional B cell repopulation.
    • Antigen-experienced B cells persisted in some non-responders; BCR diversity was transiently reduced.
    • Responders showed reduced NF-κB activation in repopulated naïve B cells and enhanced T cell activation/cytotoxicity markers in CD4 T cells and DN T cells.

    Conclusions:

    • Longitudinal single-cell profiling reveals dynamic immune cell shifts following rituximab-induced B cell depletion.
    • Distinct immune cell signatures, particularly in T cells, differentiate rituximab responders from non-responders.
    • Understanding these dynamics can inform strategies to optimize B cell depletion therapies for SLE.