Lymphoproliferation in primary sjögren's syndrome. evidence of selective expansion of a b cell subset characterized by the expression of cross‐reactive idiotypes

Abstract

Objective. To evaluate the possibility that lymphoproliferation in primary Sjogren's syndrome (SS) arises within a subset of B cells.Methods. A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross-reactive idiotypes (CRI) and anti-V, and anti-V, subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and V, subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting.Results. Paraproteins from all patients expressed an epitope associated with VJIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the VJIIbassociated CRI (detected by MAb 17-109) and the V,I-associated CRI (detected by MAb G6 and GS). None of the paraproteins expressed the V,III-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients.

Light Chain Variable (VL) Sequences of Rheumatoid Factors (RF) in Patients with Primary Sjögren's Syndrome (pSS): Moderate Contribution of Somatic Hypermutation

“…Previous studies of IgM RF L chains in RA, HID and MC RF revealed a bias towards (80-93%) rather than L chains [8,14]. Similarly, RFs in SS peripheral blood as well as the B cells infiltrating the salivary glands of SS were shown previously to be biased towards L chains [25][26][27]. The predominant usage of L chains in these RFs is also associated with a restricted utilization of V 3 family genes.…”

Anti‐CD40 plus interleukin‐4‐activated human naive B cell lines express unmutated immunoglobulin genes with intraclonal heavy chain isotype variability

“…[31] to be recognized by G6, an mAb which defines an overlapping but distinct CRI to G8 frequently present on RF paraprotein [23]. As shown in Table 1 16 mutations (1 mutation/779 bp) have been observed.…”

Paraneoplastic rheumatic syndromes

“…In general, however, this 1977 report continues to be applicable today with more recent reports detailing presentations of monoarticular and pauciarticular arthritis [7][8][9][10][11][12]. A different line of clinical research has addressed the relationship of both classical rheumatoid arthritis and Sjogren's syndrome with lymphoma [13,14]. Fortin [15] has suggested that this increasingly fruitful area of research may link basic mechanisms of immune surveillance with more current concepts of programmed cell death (apoptosis) and speculated that unifying mechanisms of pathogenesis may be elucidated in the near future.…”