Third complementarity determining region sequence analysis of low-grade bronchus-associated lymphoid tissue lymphoma: genotypic analysis reveals heterogeneity in maturation.

It has recently been suggested that autoimmunity may play a role in the pathogenesis of low-grade mucosa-associated lymphoid tissue lymphomas, but precise genotypic analysis of antigen binding sites of low-grade bronchus-associated lymphoid tissue (BALT) lymphomas has not been reported. We analyzed the third complementarity determining region (CDR3) in eight cases of low-grade BALT lymphoma by 2-step PCR and sequencing analysis. All cases showed a distinct monoclonal band (about 100 base pairs) on electrophoresis. In seven cases, a single major CDR3 sequence was identified with five to nine clones among 10 vector clones being identical; and in the remaining case, two major sequences were obtained, with four clones among nine vector clones being identical. Findings suggestive of the autoimmunity of low-grade BALT lymphoma were obtained: (1) VHDJH rearrangements in seven of the eight lymphoma cell clones were potentially functional; (2) genotypically, two lymphoma cell clones showed 60 to 74% homology with G6 positive lymphocyte clones; and (3) five lymphoma cell clones showed 61 to 71 % homology with lymphocyte clones derived from fetal liver or cord blood. In one case, the N-D-N length of the neoplastic clone was very short and lacked N nucleotides at the D-JH junction. Therefore, our study demonstrates genotypic heterogeneity in maturation in low-grade BALT lymphoma.