Comparison of myosin-reactive autoantibodies from rheumatic carditis and normal fetus

Cardiac myosin reactive autoantibodies from EBV transformed monoclonal B cells of a 20 week human fetal spleen and from 3 patients with post-streptococcal rheumatic carditis were characterized. Most antibodies from 9 fetal and 6 patient myosin-reactive B cell clones were rnultireactive (reacting with cardiac myosin,Streptococcus pyogenes, and rat cardiac myocytes) which supports a role for molecular mimicry in stimulation of these antibodies. All of the VH3 expressing patient antibodies reacted with the rod portion of myosin whereas a VH1 patient antibody reacted with the myosin head. No such pattern was found for the fetal antibodies. Fetal and patient antibodies had reduced VH CDR3 length on average and reduced light chain N region addition, characteristics generally associated with fetal B cells but also with some adult B cells. 5 of 6 myosin-reactive patient clones used VH3 whereas only 2 of 9 fetal clones used VH3, suggesting skewing from the average 50-60% VH3 gene usage found in randomly selected adult and fetal antibodies. These findings suggest that fetal and patient myosin-reactive B cell populations underwent different selective processes (possibly by antigen) causing their V gene characteristics to differ as a group from those of randomly selected B cells.