Immunoglobulin G3 subclass production by rheumatoid synovial tissue cultures.

Hoffman, Wayne L.; Goldberg, Miriam; Smiley, J. Donald

doi:10.1172/jci110424

Cited by 43 publications

(24 citation statements)

References 27 publications

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“…Our study suggests that representatives of this synovial B cell population can also be found in peripheral blood, since our hybridoma fusions were done with peripheral blood lymphocytes of patients with RA. A study by Hoffman et al (29) suggests that synovial cells from RA patients with the most active synovitis produced the most IgG3. Interestingly, the type 11 collagen-specific antibodies produced in the synovium are predominantly IgG3 (30).…”

Section: Discussionmentioning

confidence: 99%

Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding

Newkirk

Lemmo

Rauch

1990

Arthritis & Rheumatism

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We investigated the influence of carbohydrate on the binding of human rheumatoid factors (RF) to the Fc fragment of IgC. The monoclonal RF studied were derived from the serum of patients with mixed cryoglobulinemia or from hybridomas generated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. Polyclonal RF were derived from patients with RA. The carbohydrate located on the Fc fragment, regardless of whether it contained different amounts of mannose or reduced amounts of galactose, or was removed, did not affect the binding of the RF. In contrast, the isotype of the Fc was found to be critical. Two groups of hybridoma RF could be delineated. One group bound preferentially to IgCl and/or IgG2, and a second group (primarily from patients with RA) bound preferentially to IgG3 and/or IgG4. Our results indicate that the isotype of the Fc fragment, and not the extent of galactosylation, influences the binding of the RF.Human rheumatoid factors (RF), a group of antibodies to gamma globulins, are highly associated with rheumatoid arthritis (RA) (1). These antibodies have been demonstrated to bind region(s) in the Fc fragment of gamma globulins, with good evidence to suggest the Cy2-Cy3 cleft as a likely site for binding

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Section: Discussionmentioning

confidence: 99%

Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding

Newkirk

Lemmo

Rauch

1990

Arthritis & Rheumatism

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“…This could explain the deficiency of RF in autologous serum with specificity for IgG3. In this regard, IgG3 is preferentially synthesized in RSC, compared with autologous serum and normal lymphoid tissue (17), and the presence of RF-PFC in PBMC correlates with aggressive synovitis and active vasculitis in RA (2).…”

Section: Discussionmentioning

confidence: 99%

Estimation of the relative avidity of 19S IgM rheumatoid factor secreted by rheumatoid synovial cells for human IgG subclasses

Robbins

Skilling

Benisek

et al. 1986

Arthritis & Rheumatism

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19S IgM rheumatoid factors (RF) may play an important role in sustaining inflammation in rheumatoid arthritis (RA). As yet, no unique antigenic specificity for RF in RA has been identified. Because the synovium is central to the pathogenic changes in RA, RF produced therein might be pathogenically more important than serum RF. Therefore, we examined the reactivity and relative avidity of 19S IgM‐RF in serum and rheumatoid synovial cells (RSC) from 20 patients with seropositive RA. Reactivities were determined by competitive inhibition of serum RF hemolytic activity and RSC RF‐plaque‐forming cells (PFC) by added soluble antigen, i.e., monomeric human IgG subclasses. Estimation of relative avidities of RSC RF for human IgG subclasses was done by calculation of fractional RF expression in the RSC RF‐PFC assay following inhibition by IgG subclasses. RSC RF had greatest reactivity with IgG3 and IgG1, some reactivity with IgG2, and the least reactivity with IgG4. Serum RF reacted most with IgG1 and IgG2, reacted some with IgG4, but reacted poorly with IgG3. The antigenic determinants with which RSC RF reacted were common to many IgG3 molecules. The highest relative avidity of RSC RF was for IgG3. These observations indicate a selective deficiency of serum RF compared with RSC RF and suggest an important pathogenic role for these qualitatively different RSC RF molecules for in situ RF immune complex‐mediated inflammation in RA synovial tissue.

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“…This confirms the immunohistochemical findings of Mellbye et al (1984) who reported that the majority of plasma cells in 15 synovia from seropositive and eight synovia from seronegative RA patients were secreting IgGI. However, bias towards secretion of other IgG subclass in rheumatoid synovia has also been documented (Munthe & Natvig, 1972;Hoffman et al, 1982). In these cases IgG3 predominated; however, in one of these studies (Munthe & Natvig 1972) IgGI or IgG2 restriction was demonstrated in four out of nine patients where > 50% of plasma cells secreted one subclass.…”

Section: Discussionmentioning

confidence: 94%

“…Previous studies have been directed at the analysis of synovial tissue culture supernatants and histological examination of synovial tissue seetions. These studies suggest a restricted Correspondence: Christina Brown MSc, The Kennedy Institute of Rheumatology, 6 Bute Gardens, Hammersmith, London W6 7DW, UK, heterogeneity of antibodies secreted in the rheumatoid synovium, as evidenced by lambda light chain predominance (Epstein & Tan, 1966;Lindstrom, 1970;Munthe & Natvig, 1972), over-representation of particular IgG subclasses (Munthe & Natvig 1972;Hoffman, Goldberg & Smiley, 1982;Mellbye, Vartdal & Dobloug, 1984) and restriction in the isolelectric point of synovial IgG (Hoffman, Douglass & Smiley, 1984),…”

Section: Introductionmentioning

confidence: 99%

Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia

Brown

Plater-Zyberk

Mageed

et al. 1990

Clinical and Experimental Immunology

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SUMMARYTwenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA), Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-seereting hybridomas produced antibodies which belonged to the IgGl subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3; 1, All IgG antibodies were eationie, Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results refieet the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B eells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-seereting and two out of 26 IgG-secreting hybridomas produeed rheumatoid factors (RF), The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG 1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe ofthe G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG, The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%, Keywords human hybridomas synovial tissue rheumatoid arthritis immunoglobulin isotypes

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Immunoglobulin G3 subclass production by rheumatoid synovial tissue cultures.

Cited by 43 publications

References 27 publications

Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding

Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding

Estimation of the relative avidity of 19S IgM rheumatoid factor secreted by rheumatoid synovial cells for human IgG subclasses

Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia

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