SOMATIC HYPERMUTATION IN LOW-GRADE MUCOSA-ASSOCIATED LYMPHOID TISSUE-TYPE B-CELL LYMPHOMA

The origin of low-grade mucosa-associated lymphoid tissue (MALT)-type B-cell lymphoma is still unclear, Using a novel two-step procedure, we have sequenced the Ig VH genes expressed by cells from four patients with gastric low-grade MALT-type lymphoma. The nucleotide sequences of the complementarity determining region 3 (CDR3) of the genomic DNA we re first amplified using consensus oligonucleotide primers, then seque nced, Based on the CDR3 sequence amplified from each MALT lymphoma, in dividual tumor-specific primers were synthesized and used directly in the polymerase chain reaction (PCR) to analyze the sequences of their Ig heavy-chain variable region. When compared with the germ-line seque nce, many nucleotide substitutions, mainly in the CDRs, were found in the variable gene sequences of the four MALT lymphomas, The mutations showed a high replacement-to-silent ratio and were distributed in a wa y which suggested that the tumor cells had been positively selected th rough their antigen receptor, Our findings indicate that the MALT-type lymphoma B cells are hypermutated postgerminal center lymphocytes tha t have undergone antigen selection. (C) 1995 by The American Society o f Hematology.