Beyond the surface - Autoreactive B cells in human autoimmune diseases

Area of Science:

• Immunology
• Autoimmunity
• Rheumatology

Background:

• Autoreactive B and plasma cells drive autoimmune diseases.
• Autoantibodies are biomarkers and pathogenic molecules.
• Understanding B cell tolerance breaks and memory triggers is limited.

Purpose of the Study:

• Investigate human autoreactive B cell phenotype and function in disease.
• Utilize rheumatoid arthritis and post-translationally modified antigens as models.

Main Methods:

• Antigen-specific identification and multiparameter phenotyping of autoreactive B cells.
• Used conventional and spectral flow cytometry.
• Analyzed patient cohorts across disease stages, including pre-clinical and remission phases.

Main Results:

• Autoreactive B cells are activated effector memory cells in established disease, secreting cytokines and expressing homing markers.
• Pre-clinical phase shows lower activation and fewer migratory plasmablasts.
• Cells exhibit cross-reactivity to post-translational modifications and glycosylated B cell receptors.

Conclusions:

• Disease-specific autoreactive B cells show heterogeneous features reflecting disease stage.
• Rheumatoid arthritis involves germinal center-derived B cell autoreactivity with cross-reactivity and T cell dependence.
• Therapeutic strategies for B cell targeting may need to be tailored to specific autoimmune diseases.