Human B-cell clones expressing lupus nephritis-associated anti-DNA idiotypes are preferentially expanded without somatic mutation.
Human monoclonal anti-single/double-stranded (ss/ds) DNA antibodies (NE-1 and NE-13) expressed cross-reactive idiotypes (Id), NE-1 Id, which have been detected on the lupus glomeruli-deposited anti-DNA antibodies. The nucleotide sequences of the variable regions of NE-1 and NE-13 clones were analogous except for one nucleotide difference in the Vk region. The VH and Vk gene segments of NE-13 clone were identical with germline genes VH4.21 and Vb (or Vb'), respectively. CDR3s of NE-1 and NE-13 heavy chains were arginine rich and CDR1s contained an amino acid stretch, SGYY, the inverted sequence of YYGS, which was shared among CDR3s of several anti-DNA antibodies. Clonal frequency analysis using a limiting dilution method revealed that NE-1 Id-positive clones at precursor cell level increased in lupus patients. These findings suggest that some IgM anti-DNA clones which express NE-1 Id associated with lupus nephritis use germline genes without mutation and they may be preferentially expanded at the precursor cell levels as well as at the mature cell level.
Hirabayashi
Y
Y
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Munakata
Y
Y
Takai
O
O
Shibata
S
S
Sasaki
T
T
Sano
H
H
D000293:Adolescent; D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002999:Clone Cells; D003429:Cross Reactions; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M