A B cell explanation for autoimmune disease: the forbidden clone returns

Area of Science:

• Immunology
• Autoimmunity
• Cell Biology

Background:

• The 'forbidden clone' hypothesis suggests autoimmune diseases stem from self-reactive lymphocyte clones escaping immune tolerance.
• Evidence increasingly implicates B cell precursors in the pathogenesis of autoimmune disorders.

Purpose of the Study:

• To review and synthesize evidence supporting the 'forbidden clone' hypothesis, focusing on the role of B cells in autoimmunity.
• To highlight the therapeutic implications of targeting B cells in various autoimmune diseases.

Main Methods:

• Review of existing literature and clinical evidence across multiple medical specialties.
• Analysis of the efficacy of B cell-depleting therapies in diverse autoimmune conditions.
• Examination of findings related to B cell clonality and autoantibody production in autoimmune diseases.

Main Results:

• B cell-depleting therapies have demonstrated success in rheumatoid arthritis, ANCA-associated vasculitis, polymyositis, lupus, multiple sclerosis, and idiopathic thrombocytopenic purpura.
• Clonality in B cells and plasma cells is observed in numerous autoimmune disorders.
• Autoantibodies can precede clinical disease onset, indicating early autoreactivity within the B cell lineage.

Conclusions:

• The persistence of autoreactive B cell clones is a strong candidate mechanism for autoimmune disease development.
• Targeting B cells offers a promising therapeutic strategy for a wide spectrum of autoimmune conditions.
• Understanding B cell-mediated autoimmunity provides insights into disease pathogenesis and potential interventions.