Somatic mutation in autoantibody-associated VH genes of circulating IgM+IgD+ B cells.
Naive B cells expressing IgM and IgD on their surface have no or little somatic mutations in V genes. We have demonstrated that the human IgM+IgD+B cell clone (0-81), which expresses nephritogenic idiotypes, produces IgM anti-DNA antibodies which show monospecificity to DNA. Using a DNA probe which specifically links to the VH gene of antibody 0-81, we identified the counterpart germ-line V gene of 0-81, V3-7, which appears to be used by pathogenic autoantibodies in humans. Clone 0-81, which may belong to naive B cells in terms of cell phenotype, uses a somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in circulating IgM+IgD+B cells from normal subjects and patients with systemic lupus erythematosus (SLE). The results revealed that rearranged V3-7 genes in IgM+IgD+B cells from patients with SLE contained somatically mutated sequences at significantly increased frequencies. These data indicate an abnormal maturation of B cells in autoimmune states that may be associated with an escape of self-reactive B cells from the elimination process in the germinal center.
Munakata
Y
Y
The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Saito
S
S
Hoshino
A
A
Muryoi
T
T
Hirabayashi
Y
Y
Shibata
S
S
Miura
T
T
Ishii
T
T
Funato
T
T
Sasaki
T
T
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D001483:Base Sequence; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D005854:Germ Cells / Q000276:immunology; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000097:blood / Q000235:genetics*; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*
D001323:Autoantibodies; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region