DNA sequence of immunoglobulin heavy chain variable region gene in thyroid lymphoma.
Patho-epidemiological studies have shown that thyroid lymphoma (TL) develops in thyroid affected by chronic lymphocytic thyroiditis (CLTH). CLTH is categorized as an organ-specific autoimmune disease, in which activated B-lymphocytes secrete a number of autoantibodies. Because antigenic stimulation might be involved in the pathogenesis of TL, the variable region in heavy chain (V(H)) genes was characterized in 13 cases with TL and 3 with CLTH. Clonal rearrangement of the V(H) gene was found in 11 cases of TL, and cloning study with sequencing of complimentary determining region (CDR) 3 revealed the presence of a major clone in 4. Three of the 4 cases used V(H) 3 gene, with the homologous germline gene of V3-30 in two cases and VH26 in one case. A biased usage of V(H) 3 and V(H) 4 genes with the homologous germline gene of VH26 in V(H) 3 gene was reported previously in cases with CLTH. A high level of somatic mutation (1-21%, average 12%) with non-random distribution of replacement and silent mutations was accumulated in all cases. The frequency of the occurrence of minor clones ranged from 29-44% per case, indicating the presence of on-going mutation. DNA sequencing of immunoglobulin V(H) gene suggests that TL develops among activated lymphoid cells in CLTH at the germinal center stage under antigen selection.
Miwa
H
H
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871.
Takakuwa
T
T
Nakatsuka
S
S
Tomita
Y
Y
Matsuzuka
F
F
Aozasa
K
K
D018528:ATP-Binding Cassette Transporters; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002999:Clone Cells / Q000378:metabolism; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007125:Immunogenetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000276:immunology*
D018528:ATP-Binding Cassette Transporters; C109399:Cdr3 protein, Candida albicans; D022801:Complementarity Determining Regions; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region