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 were first amplified using consensus oligonucleotide primers, then sequenced. Based on the CDR3 sequence amplified from each MALT lymphoma, individual 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 sequence, 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 way which suggested that the tumor cells had been positively selected through their antigen receptor. Our findings indicate that the MALT-type lymphoma B cells are hypermutated postgerminal center lymphocytes that have undergone antigen selection.
Qin
Y
Y
Pathologisches Institut, Julius Maximilians Universität Würzburg, Deutschland.
Greiner
A
A
Trunk
M J
MJ
Schmausser
B
B
Ott
M M
MM
Müller-Hermelink
H K
HK
D000595:Amino Acid Sequence; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region