IgG2b inducing factor from rheumatoid arthritis synovial fluid synergizes with transforming growth factor-beta in...

Rheumatoid arthritis synovial fluid (RA-SF) contains a distinct biological activity that selectively induces IgG2b production in LPS-activated murine B blasts. This IgG2b inducing factor (IgG2bIF) acts directly on purified LPS-activated B blasts from normal and Bruton's tyrosine kinase-defective CBA/N mice. In order to test the possibility that TGF-beta and IgG2bIF in RA-SF act in concert to induce IgG2b production, anti-TGF-beta monoclonal antibodies and RA-SF were added to LPS-activated CBA B blasts, which led to a marked reduction of IgG2b-producing cells. This result indicates that TGF-beta and IgG2bIF in RA-SF synergize in the induction of IgG2b production. TGF-beta antibodies do not inhibit IgG2b production in CBA/N B blasts, further substantiating our earlier notion that CBA/N B blasts have a higher endogenous production of TGF-beta after LPS stimulation, which might be responsible for the aberrant reactivity in btk deficient CBA/N mice. RA-SF is able to reconstitute the deficient IgG1 response in LPS- and IL-4-stimulated CBA/N B blasts. Addition of antibodies against TGF-beta had only a marginal effect on the IgG1 response, indicating that the reconstitution is mediated by another factor(s), which is present in RA-SF.