Myosin-reactive autoantibodies in rheumatic carditis and normal fetus.
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 VH CDR3 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 VH3, whereas only two of nine fetal clones used VH3, suggesting skewing from the average 50-60% VH3 gene usage found in randomly selected adult and fetal antibodies.
Wu
X
X
Department of Pathology, University of Texas Houston Health Science Center, Houston 77030, USA.
Liu
B
B
Van der Merwe
P L
PL
Kalis
N N
NN
Berney
S M
SM
Young
D C
DC
D000328:Adult; D000368:Aged; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003429:Cross Reactions; D005312:Fetal Blood / Q000276:immunology; D005333:Fetus / Q000276:immunology*; D006801:Humans; D009205:Myocarditis / Q000097:blood / Q000276:immunology*; D009218:Myosins / Q000276:immunology*; D051381:Rats; D012214:Rheumatic Heart Disease / Q000097:blood / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology
D000942:Antigens, Bacterial; D001323:Autoantibodies; D009218:Myosins