Synovial Fluid from Rheumatoid Arthritis Patients Induces Polyclonal Antibody Formation in Vivo

Our previous studies demonstrated the presence of a T‐cell replacing factor in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and that RA‐SF can activate, selectively, the induction of IgG2b antibody secreting cells, in lipopolysaccharide (LPS)‐pretreated mouse spleen cell cultures. In the present study the effect of RA‐SF was tested in vivo in mice. Injection of the polyclonal activator LPS induced the production of IgM and IgG3 secreting cells in normal mice. However, the addition of RA‐SF led to a selective increase in the production of IgG2b with a peak response on day Sand IgG1 plaque‐forming cells (PFC) with a peak on day 7. Neither the IgG2b nor IgG1 responses were caused by specific immunity against heterologous proteins present in RA‐SF, as injection of in vitro inactive RA‐SF samples did not induce PFC. The effect on B cells of RA‐SF was further evaluated by injection of RA‐SF in combination with LPS to the Xid B‐cell deficient CBA/N mice, RA‐SF had identical effects in CBA/N as in normal mice. The biological implication of these findings is discussed. Our earlier results support the idea that B cells are endogeneously activated in RA patients, We have speculated that this activation is caused by the B‐cell differentiation factor which is present in SF. Therefore, we also tested whether RA‐SF could influence antibody‐forming cells in mice that spontaneously develop autoimmunity. We found that injection of RA‐SF alone, in the absence of any other activating substance, induced a very marked increase of IgG producing cells in (NZW × NZB) F1 hybrid mice. From a relatively high background level the RA‐SF could still induce an up to 100‐fold increase in the numbers of PFC in spleens of such mice.