Immunoglobulin VH genes in thymic MALT lymphoma are biased toward a restricted repertoire and are frequently unmutated.
Thymic MALT lymphoma shows certain distinctive features among MALT lymphomas, such as expression of IgA isotype, consistent lack of API2-MALT1 gene fusion, and very strong association with autoimmune disease, especially Sjogren's syndrome. To help clarify the nature of the clonal lymphoid infiltrates, we analysed the usage and somatic hypermutation of the Ig heavy chain variable region (V(H)) genes in nine different cases. The V(H) rearrangement was potentially functional in all cases and was restricted to the V(H)3 family. V(H) usage was biased toward V(H)3-30 (five cases) and V(H)3-23 (three cases) segments, which have both been frequently expressed by autoimmune B cells. Somatic hypermutation was absent in five cases. Fewer than the expected replacement mutations were found in the framework regions in two cases, indicating a negative antigen selection pressure. Ongoing mutation was absent in all cases. D segment usage was varied, whereas J(H) segment usage was restricted to J(H)4. The observed patterns of V(H) usage and mutations suggested that specific antigens may play a pathologically relevant role in the genesis or progression of thymic MALT lymphoma.
Yoshida
Megumi
M
Department of Pathology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Okabe
Mitsukuni
M
Eimoto
Tadaaki
T
Shimizu
Shinichiro
S
Ueda-Otsuka
Kayo
K
Okamoto
Masataka
M
Ishii
Genichiro
G
Ueda
Ryuzo
R
Chan
John K C
JK
Nakamura
Shigeo
S
Inagaki
Hiroshi
H
D000368:Aged; D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology*
D000941:Antigens; D022801:Complementarity Determining Regions