IgG2b inducing factor from rheumatoid arthritis synovial fluid activates antibody production in highly purified mouse...

Rheumatoid arthritis synovial fluid (RA-SF) contains a factor that induces IgG2b antibody production in LPS-stimulated murine B cells and therefore is called IgG2b inducing factor (IgG2bIF). When LPS, together with crude RA-SF or semi-purified IgG2bIF, was added to highly purified LPS-stimulated B cells, the number of IgG2b-producing cells was substantially enhanced. This shows that IgG2bIF acts directly on activated B cells, presumably by binding to a receptor expressed on LPS-activated B cells. In vivo LPS-activated B blasts were not able to respond to RA-SF unless LPS was present in vitro, showing that LPS is needed to maintain cell viability and responsiveness to the IgG2bIF. To elucidate the mechanism for the IgG2bIF effect on highly purified B cells, the IgG2b response of LPS-stimulated, Bruton's tyrosine kinase-defective, xidB blasts was studied. Purified B blasts from the btk-defective CBA/N mouse strain were sensitive to IgG2bIF. These findings show that IgG2bIF acts directly on B cells and activates cells through a btk-independent pathway.