Rearrangement of the Rheumatoid Factor-Related Germline Gene Vg and bcl-2 Expression in Lymphoproliferative Disorders in Patients with Sjögren's Syndrome

Impact of Gender on Exocrine Gland Inflammation in Mouse Models of Sjögren's Syndrome

“…Insertion of the bcl-2 transgene into B6\lpr mice is known to significantly augment lymphadenopathy and T cell accumulation in lymphatic tissues (Reap et al, 1995). Moreover, the expression of bcl-2 is : (a) up-regulated in circulating lymphocytes of patients with Sjo$ gren's syndrome and SLE (Gatenby and Irvine, 1994 ;Ohsako et al, 1994 ;Sugai et al, 1994) ; (b) significantly influenced by gender in lacrimal glands of mouse models of Sjo$ gren's syndrome ; and (c) believed to play a critical role in promoting the inflammatory process and the programmed cell death of epithelial cells in autoimmune exocrine tissues (Kong et al, 1997a).…”

Possible Mechanisms of Lymphoma Development in Sjogren’s Syndrome

“…Immunoglobulin generation occurs early during B cell development in the bone marrow. During later steps of B cell development, immunoglobulin undergo recombination, somatic mutation and isotype switching, events that require breaking and reconnecting DNA, increasing the risk of chromosome translocation of oncogenes, such as Bcl-2 and c-Myc, to immunoglobulin loci on chromosome 14q32 [64]. Mutagenesis during these processes may result in the generation of B cells with defective apoptosis and enhanced proliferation, favoring lymphoma development [43].…”

“…Evidence of defective repair of a pro-mutagenic DNA base lesion, O6-methylguanine, has been observed in the lymphocytes of patients with pSS predisposed to lymphoma [91], suggesting that these patients may have defective DNA repair mechanisms. Other genetic events, such as bcl-2 or c-Myc amplification, trisomy 3 or 18, may facilitate the progression of low-grade MALT lymphoma to a more malignant high-grade lymphoma [43, 48, 64, 91, 92]. Activation of the enzyme cytidine deaminase (AID) has been associated with somatic hypermutation and class switch recombination [65].…”

Sjogrens Syndrome and Lymphoma Development

“…Hansen, et al found that the proportion of B cells expressing mutated V(H) genes was significantly higher in B-cells isolated from the parotid gland compared with circulating B cells. These events require breaking and reconnecting DNA, subsequently increasing the risk of chromosome translocation of oncogenes such as Bcl-2 [42] and c-Myc to immunoglobulin loci (chromosome 14q32). As we know, immunoglobulin generation occurs early in the development of B cells in the bone marrow.…”

“…Pisa, et al found high frequency of t (14,18) translocation in salivary gland lymphoma from SS patients [57]. Other genetic events such as bcl-2 [42], c-Myc amplification or trisomy 3 may facilitate the progression of low-grade MALT lymphoma to a more malignant high-grade lymphoma [32,33]. This raised the possibility that pSS patients predisposed to lymphoma may have defective DNA repair mechanisms.…”