Monospecific but not polyreactive human hybridoma rheumatoid factors exhibit preferential binding specificities for IgG3 and IgG4

Abstract

Among 38 human hybridoma-derived monoclonal rheumatoid factors (RFs) generated from patients with either rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), two groups of RFs can be identified. Monospecific RFs were derived primarily from patients with RA and are characterized by a binding specificity for IgG3 and/or IgG4. Polyreactive RFs were derived largely from patients with SLE and show a broader pattern of reactivity to all four isotypes of IgG. Neither population of RFs was exclusive to either disease. The binding specificities identified appear to be different from the RFs isolated from patients with mixed cryoglobulinemia and may reflect a different antigen selection mechanism.

Rheumatoid Factors: Host Resistance or Autoimmunity?

“…From limiting dilution studies of the peripheral blood B-cell pool, IgM RF expressing B-cells are present in normal individuals at a frequency of 0.9% (of total B-cells) and in RA patients at a frequency of 1.48% (143). Although the frequencies in peripheral blood are fairly similar, the RFs in RA are monospecific, whereas in normal individuals they are polyreactive (143,144). In synovial fluid the RF-committed B-cell frequency in seropositive patients is 10-fold higher (145).…”

A Human Rheumatoid Factor C304 Shares VH and VL Gene Usage with Antibodies Specific for Ubiquitous Human Viral Pathogens

“…This was demonstrated when the C304 antibody was shown to have anti-human IgG Fc (RF) activity but no anti-dDNA, anti-PL, anti-CL, anti-DOPE or Coombs reactivities (data not shown). In addition, we have demonstrated that C304 RF has the 'Ga' pattern of IgG isotype binding, with maximal binding to IgGI isotype [19]. Furthermore, competitive inhibition studies, using soluble IgGI Fc fragments, demonstrated that C304 has a Kj value of 6.7 X 10~* M for the IgGI isotype (data not shown).…”