The Studies on the Early Phase of Mlignant Lymphoma in Patients with Sjogren's Syndrome

(1)免疫球蛋白VL基因的单克隆性研究干燥综合征(SS)患者的SF18/2独特型常见于SS患者的血清和外周血淋巴细胞表面(1)。我们证明该SF18/2独特型是VK III亚组成员的VG胚系基因的产物(2)。然后，我们对SS患者外周血白细胞DNA样本中VG基因重排进行了研究。在87%的SS患者中检测到274kb的重排片段。序列分析表明，1个片段与VG生殖系基因有98.5%的同源性，另一个与CDR3区的8个替换突变有95.8%的同源性。认为VG胚系基因的高频率重排是SS患者发生淋巴增殖的因素之一。(2)免疫球蛋白VH-CDR3基因的单克隆性研究对50例SS患者的SY标本和IgVH-CDR3区进行半套式聚合酶链式反应，在50例SS患者的唇部活检标本中，有7例出现了单克隆或寡克隆条带(4)。6例SS患者的主要唾液腺出现结节。这些结节已被手术切除，并被证实为病理良性。6个样本中有4个出现了单克隆带。这些条带的亚克隆和测序显示了来自不同患者的2个共同的DNA序列。这些序列与恶性淋巴瘤或骨髓瘤患者中报道的基因有密切的同源性(5)。在2例泪腺肿大的4例泪腺标本中，有3例出现单克隆带(6)。这些样本的DNA序列与唾液腺中发现的DNA序列不同。提示B细胞在小涎腺或大涎腺和泪腺的慢性炎症部位发生了单克隆性增殖，并在SS患者中发展为恶性。较少

(1)Studies on the monoclonality of Ig VL genesSF18/2 idiotype derived from a patient with Sjogren's syndrome (SS) was frequently detected in sera and on the surface membrane of the peripheral blood lymphocytes from SS patients (1). We proved that this SF18/2 idiotype was a product of the Vg germline gene which is a member of the VK III subgroup (2). Then, we studied the rearrangement of the Vg gene in DNA samples from the peripheral blood leukocytes from SS patients. The rearranged 274kb fragments were detected in 87% of SS patients. By sequencing these fragments, it was shown that one has the 98.5% homology to the Vg germline gene and another has the 95.8% homology with 8 replacement mutations in the CDR3 region (3). It was considered that the high frequency of the rearrangement of the Vg germline gene is one of the factors to trigger the development of lymphoproliferation in SS patients.(2)Studies on the monoclonality of Ig VH-CDR3 genesThe DNA samples were prepared from the lip biop … More sy specimens of 50 SS patients and the IgVH-CDR3 regions were amplified by seminested PCR using appropriate primers.Among 50 samples of the lip biopsy from SS patients, 7 showed monoclonal or oligoclonal bands (4). Six patients with SS developed nodules in their major salivary glands. These nodules had been resected surgically and were proved to be pathologically benign. Four out of 6 samples showed monoclonal bands. The subcloning and sequencing of these bands showed 2 common DNA sequences from different patients. These sequences had the close homology to those genes reported in patients with malignant lymphoma or myeloma (5). Among 4 samples from lachrymal glands from 2 patients who showed swollen lachrymal glands, 3 showed monoclonal bands (6). The DNA sequences of these samples were different from those found in salivary glands. These data indicate that B cell monoclonal proliferation occurs in the chronic inflammation sites in minor or major salivary glands and lachrymal glands and develops to be malignant in patients with SS. Less