MYOSIN-REACTIVE AUTOANTIBODIES IN RHEUMATIC CARDITIS AND NORMAL FETUS

EBV-transformed B cells from it 20-week human fetal spleen and from bl ood of patients with poststreptococcal rheumatic carditis were studied . Most antibodies from nine fetal and six patient myosin-reactive B ce ll clones were multireactive (reacting with cardiac myosin, Streptococ cus pyogenes, and rat cardiac myocytes) which supports a role for mole cular mimicry in stimulation of these autoantibodies. Sequence analysi s revealed that fetal and patient anti-myosin repertoires were compose d of unrelated clones with diverse V gene usages, Fetal and patient an tibodies lead reduced V-H CDR3 length on average and reduced light cha in N region addition with a low rate of somatic mutation in the variab le region genes, characteristics generally associated with fetal B cel ls but also with some adult B cells. Five of six myosin-reactive patie nt clones used V(H)3, whereas only two of nine fetal clones used V(H)3 , suggesting skewing from the average 50-60% V(H)3 gene usage found in randomly selected adult and fetal antibodies. (C) 1998 Academic Press .