Pathogenic autoantibodies and B-cell receptors

Pathogenic autoantibodies and B-cell receptors (BCRs) constitute a primary axis in the development of autoimmune disorders and B-cell malignancies. Pathogenic autoantibodies are self-reactive immunoglobulins that cause tissue damage or organ dysfunction by binding to self-antigens, such as the acetylcholine receptor in myasthenia gravis or desmogleins in pemphigus [StatPearls, PubMed]. The B-cell receptor is a multi-protein complex on the surface of B cells that recognizes antigens and initiates intracellular signaling pathways, such as the Bruton's tyrosine kinase (BTK) pathway, which are essential for B-cell development and antibody production [UniProt, PubMed]. In autoimmune conditions like myasthenia gravis and systemic lupus erythematosus, the production of these autoantibodies is driven by dysregulated BCR signaling and B-cell activation [PubMed, StatPearls]. Therapeutic interventions targeting this axis include FcRn inhibitors (e.g., efgartigimod) which accelerate the clearance of pathogenic IgG, BTK inhibitors (e.g., ibrutinib) which disrupt BCR signaling, and B-cell depleting agents (e.g., rituximab) that eliminate the cellular source of autoantibodies [argenx, PubMed]. These therapies are essential for managing conditions where the immune system mistakenly attacks host tissues or where B cells undergo malignant transformation [StatPearls].

Other names

Autoreactive B-cell receptorsSelf-reactive antibodiesAutoimmune B-cell axisPathogenic IgGB-cell antigen receptor complexaAb

Neonatal Fc receptor (FcRn) antagonism to reduce circulating IgG; Bruton's tyrosine kinase (BTK) inhibition to disrupt B-cell receptor signaling; B-cell depletion via monoclonal antibodies targeting CD20, CD19, or CD79b.