Lessons from an anti-DNA autoantibody

R4A is an anti-DNA antibody derived by hybridoma technology from a BALB/c mouse. The study of its properties has helped to elucidate aspects of the physiopathology of Systemic Lupus Erythematosus (SLE). It has been useful to decipher the mechanisms implicated in breaks in B cell self tolerance by B cell extrinsic or B cell intrinsic factors. Furthermore, it illustrates the importance of molecular mimicry in understanding the cellular and molecular effects relevant to some manifestations of neuropsychiatric lupus, as it cross-reacts with the D/E W D/E YS/G peptide sequence present in subunits of the N-methyl d-aspartate receptor (NMDAR).

Research highlights▶ A subset of anti-DNA antibodies contributes to CNS lupus. ▶ B cell receptor signal strength is governed by B cell intrinsic and extrinsic factors. ▶ Low B cell receptor signal strength in transitional B cells predisposes to autoimmunity.