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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
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Balancing Act: The Dual Roles of BAFF in Systemic Lupus Erythematosus
Jhonatan Antonio Álvarez-Gómez1, Daniel Appelgren2, Tomas Walhelm3
1Division of Inflammation & Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. jhonatan.antonio.alvarez.gomez@liu.se.
Drugs
|July 21, 2026
Summary
B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are key in autoimmune diseases. This review examines their complex role in regulatory B cells and the effectiveness of therapies targeting them.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are crucial cytokines in regulating B cell survival and differentiation in autoimmune diseases like systemic lupus erythematosus (SLE).
- These cytokines interact with receptors BAFF-Receptor (BAFF-R), TACI, and BCMA, influencing self-reactive B cells and antibody production.
- Current biologic therapies targeting BAFF/APRIL show variable efficacy and safety profiles, with some cases of de novo lupus nephritis observed despite treatment.
Purpose of the Study:
- To review current evidence on anti-BAFF/APRIL therapies in autoimmune diseases.
- To explore the complex and potentially context-dependent role of BAFF in the function and development of regulatory B cells (Bregs).
- To address the unresolved question of whether BAFF's involvement in regulatory immune responses is beneficial or detrimental.
Main Methods:
- Literature review of existing studies on BAFF, APRIL, and their targeted therapies.
- Analysis of clinical trial data and observational studies concerning belimumab and other anti-BAFF/APRIL agents.
- Examination of the molecular interactions between BAFF/APRIL, their receptors, and B cell subsets, including Bregs.
Main Results:
- Anti-BAFF/APRIL therapies can lead to profound B cell suppression and reduced immunoglobulin production.
- Belimumab has shown efficacy in SLE but has been associated with de novo lupus nephritis in some patients.
- Belimumab treatment correlates with reduced regulatory B cell markers and IL-10 levels, suggesting a role for BAFF in Breg function.
Conclusions:
- The precise role of BAFF in supporting regulatory B cell function remains complex and requires further elucidation.
- Understanding BAFF's context-dependent effects is critical for optimizing therapeutic strategies in autoimmune diseases.
- Further research is needed to fully unravel the intricate interplay between BAFF, APRIL, and the regulatory immune system.
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