B-cell tolerance breakdown in Sjögren's syndrome: focus on BAFF

Area of Science:

• Immunology
• Autoimmunity
• Rheumatology

Background:

• Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by epithelial cell destruction and lymphocytic infiltration of exocrine glands.
• B cells play a significant role in SS pathogenesis, with B cell activating factor (BAFF) being a key implicated cytokine.
• BAFF overexpression is observed in SS and linked to B cell tolerance breakdown and autoantibody production.

Purpose of the Study:

• To elucidate the role of BAFF in Sjögren's syndrome pathogenesis.
• To investigate BAFF's impact on B cell subsets, tolerance, and autoantibody production in SS.
• To understand BAFF's contribution to B cell repopulation after therapeutic B cell depletion.

Main Methods:

• Analysis of BAFF expression in SS patients.
• Evaluation of B cell populations and distribution in blood and salivary glands.
• Assessment of BAFF's role in B cell tolerance and autoantibody production.
• Investigation of BAFF's influence on B cell repopulation post-rituximab treatment.

Main Results:

• BAFF overexpression in SS is associated with the emergence of self-reactive B cells and B cell hyperactivity.
• Abnormal distribution of B cell subsets, including transitional type 2 (T2) and marginal-zone (MZ)-like B cells, is observed in SS patients.
• BAFF contributes to the expansion of autoreactive T2 and MZ-like B cells within salivary glands.
• BAFF is crucial for B cell repopulation following rituximab-induced depletion in SS.

Conclusions:

• BAFF is a central mediator in Sjögren's syndrome pathogenesis, driving B cell autoimmunity.
• Targeting BAFF may represent a therapeutic strategy for SS by modulating B cell responses.
• Understanding BAFF's role in B cell dynamics is critical for developing effective SS treatments.