Myosin-Reactive Autoantibodies in Rheumatic Carditis and Normal Fetus

Abstract

EBV-transformed B cells from a 20-week human fetal spleen and from blood of patients with poststreptococcal rheumatic carditis were studied. Most antibodies from nine fetal and six patient myosin-reactive B cell clones were multireactive (reacting with cardiac myosin,Streptococcus pyogenes,and rat cardiac myocytes) which supports a role for molecular mimicry in stimulation of these autoantibodies. Sequence analysis revealed that fetal and patient anti-myosin repertoires were composed of unrelated clones with diverse V gene usages. Fetal and patient antibodies had reduced V_HCDR3 length on average and reduced light chain N region addition with a low rate of somatic mutation in the variable region genes, characteristics generally associated with fetal B cells but also with some adult B cells. Five of six myosin-reactive patient clones used V_H3, whereas only two of nine fetal clones used V_H3, suggesting skewing from the average 50–60% V_H3 gene usage found in randomly selected adult and fetal antibodies.