Analysis of lymphoproliferative disorders of Sjogren's syndrome

Research Project

Project/Area Number	06454531
Research Category	Grant-in-Aid for General Scientific Research (B)
Allocation Type	Single-year Grants
Research Field	病態科学系歯学(含放射線系歯学)
Research Institution	Tokyo Medical and Dental University
Principal Investigator	SAITO Ichiro Division of Immunological Diseases, Medical Research Institute, Tokyo Medical and Dental University Associate Professor, 難治疾患研究所, 助教授 (60147634)
Co-Investigator(Kenkyū-buntansha)	宮坂信之東京医科歯科大学, 難治疾患研究所, 教授 (30157622)
Project Period (FY)	1994 – 1995
Project Status	Completed (Fiscal Year 1995)
Budget Amount *help	¥7,100,000 (Direct Cost: ¥7,100,000) Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000) Fiscal Year 1994: ¥4,700,000 (Direct Cost: ¥4,700,000)
Keywords	Sjogren's syndrome / Lymphoproliferative disorders / Bcl-2 / Epstein-Barr virus / latent membrane protein-1 / apoptosis
Research Abstract	Lymphoproliferative disorders (LPD) known to occur in Sjogren's syndrome (SS), with which a correlation to Epstein-Barr virus (EBV) has been suggested, but the mechanism of development remains to be clarified. LPD which show no chromosomal translocation t (14 ; 18) or inactivation of tumor suppressor genes, have been suggested to develop by suppression of apoptosis via an as yet undefined mechanism. Some reports have recently shown a mechanism, by which EVB-infected cells can avoid apoptosis, which involves the expression of Bcl-2 via latent membrane protein-1 (LMP-1) of EBV.In order to clarify the mechanism of LPD development in SS,LPD wa reproduce by injected SS-BCL (B cell line established from SS patient), LCL (lymphoblastoid cell line) and Raji (Burkitt's lymphoma cell line) into SCID mice for analysis of LPD.The present study revealed tendencies of SS-BCL and LCL to resist apoptosis by DNA fragmentation analysis. A comparison cell lines established from tumor tissues of SCID mice with SS-BCL and LCL showed that resistance was increased. These result suggest that the mechanism of apoptosis suppression is involved in tumor formation in mice with these cell lines. The cellular proliferative activity with Raji, during culture in 10% serum, was markedly greater than those of SS-BCL and LCL,suggesting that tumor formation with Raji is attributable to cell proliferation. These results showed differences in the mechanism of development of LPD according to differences among cell types. With regard to the expression of Bcl-2 with SS-BCL and LCL,which resisted apoptosis, this expression was marked only with SS-BCL suggesting that the mechanism of apoptosis suppression involves Bcl-2. In the present PCR assay, B region in LMP gene was selectively detected in SS-BCL.These results suggest that B cells infected with EVB of SS-BCL,which have a specific LMP sequence, might have induced Bcl-2 expression and suppressed apoptosis.