What this means
Persistent autoantibody production after conventional immunosuppression or B-cell depletion has focused attention on antibody-secreting cells that survive without ongoing proliferation. Long-lived plasma cells (LLPCs) are indispensable for durable protective immunity, but autoreactive members of this compartment may also maintain pathogenic antibodies in selected autoimmune diseases.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Earlier studies
- Kind of research
- A summary of earlier studies
The science
- Original title
- Long-lived plasma cells in rheumatic and selected antibody-mediated autoimmune diseases: biology, evidence, and therapeutic opportunities.
- Authors
- Guo H, Xiang W, Zeng L et al.
- Journal
- Autoimmunity reviews
- Published
- Oct 20, 2026
- Study type
- Review
- PMID
- 42901256 ↗
Abstract
Persistent autoantibody production after conventional immunosuppression or B-cell depletion has focused attention on antibody-secreting cells that survive without ongoing proliferation. Long-lived plasma cells (LLPCs) are indispensable for durable protective immunity, but autoreactive members of this compartment may also maintain pathogenic antibodies in selected autoimmune diseases. Interpretation is complicated because longevity is usually inferred from population kinetics, anatomical persistence, transcriptional state, or treatment resistance rather than demonstrated by lineage tracing in humans; neither CD19 loss nor any single surface phenotype is a definitive identifier. We conducted a structured narrative review focused on rheumatic diseases and selected antibody-mediated disorders. We integrate developmental routes, CXCR4-dependent homing, adhesion, BAFF/APRIL receptor biology, stromal contact, proteostatic and metabolic adaptation, and single-cell heterogeneity. Systemic lupus erythematosus and lupus nephritis receive dedicated consideration because renal antibody-secreting-cell signatures distinguish active plasmablast-rich inflammation from LLPC-like persistence in refractory disease. Across diseases, the evidence ranges from direct kinetic or tissue studies to indirect serological observations and therapeutic inference. Plasma-cell-directed therapies-including proteasome inhibition, CD38 depletion, BCMA-directed T-cell engagers or cellular therapy, and immune reconstitution-have produced clinically important signals, but most autoimmune data remain uncontrolled, early-phase, or disease-specific. Niche disruption, apoptosis or autophagy inhibition, and antigen-specific deletion remain preclinical or conceptual. A useful translational framework is therefore not that LLPCs are universal master drivers, but that persistent autoreactive plasma cells may constitute one treatment-relevant disease module whose importance should be demonstrated with tissue, clonal, and longitudinal evidence before intervention.
Guo H, Xiang W, Zeng L et al. Long-lived plasma cells in rheumatic and selected antibody-mediated autoimmune diseases: biology, evidence, and therapeutic opportunities. Autoimmunity reviews. 2026. doi:10.1016/j.autrev.2026.104198. PMID: 42901256. https://pubmed.ncbi.nlm.nih.gov/42901256/