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 complimen–tarity 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