Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjögren's syndrome.
Of 250 patients with Sjögren's syndrome (SS) (190 with 1 degree SS and 60 with 2 degrees SS), 60 patients demonstrated lymphoproliferative disorders (LPD): 41 patients had monoclonal gammopathy (MG), 4 had pseudolymphoma, 3 had in situ monoclonal lymphoproliferation, and 12 had malignant lymphoma. Rearrangement of the rheumatoid factor (RF)-related germline gene Vg (associated with the monoclonal RF SF18/2) was demonstrated in 24 of 50 genomic DNAs from the peripheral blood leukocytes of SS patients. It was found in none of 20 DNAs from normal subjects. This suggests an almost 50% incidence of a germline Ig gene rearrangement in SS patients without clinical MG. Lymphocytes composing the lymphoepithelial lesion (LEL) in the major salivary glands of SS patients expressed the oncogene bcl-2 protein in 4 out of 6 patients. The progression of SS from benign to malignant lymphoproliferation may be related to suppression of apoptotic death by bcl-2. These findings suggest that (i) RF clones are activated in SS with little or no somatic mutation resulting in monoclonal proliferation and (ii) the LEL in the salivary gland is one site for monoclonal B cell proliferation and emerging malignant lymphoma.
Sugai
S
S
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Saito
I
I
Masaki
Y
Y
Takeshita
S
S
Shimizu
S
S
Tachibana
J
J
Miyasaka
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012217:Rheumatoid Factor / Q000235:genetics*; D012469:Salivary Glands / Q000166:cytology / Q000502:physiology; D012859:Sjogren's Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA; D012217:Rheumatoid Factor