Background and Purpose: BAFF, B cell stimulating factor, is involved in the pathogenesis of primary Sjögren's syndrome (pSS) which is often accompanied by hypergammaglobulinemia. In our previous study, we found that BAFF robustly increased IL-6 production by pSS peripheral monocytes, and the expression level of a BAFF receptor (BR3) was significantly elevated in pSS monocytes compared to that of normal monocytes, suggesting that the elevated expression of BR3 is involved in activation of monocytes to promote IL-6 production. Since IL-6 promotes the differentiation of B cells, our findings may provide clues to elucidate the mechanism of the development of pSS. In this study, we investigated the possible involvement of monocytes producing IL-6 in IgG production by B cells.
Methods : Peripheral monocytes were co-cultured with B cells in the presence of soluble BAFF (sBAFF) and an anti-human sIL-6R antibody. B cells and monocytes were either directly mixed or separated with a transwell insert in the well. The amounts of IL-6 and IgG in the culture supernatants were measured by ELISA.
Results : The serum level of IgG and the proportion of BR3 positive monocytes (BR3+/CD14+) were elevated in pSS patients as compared to those in normal individuals. Remarkably, the BR3+/CD14+ ratio was positively and significantly correlated with the amount of IL-6 produced by pSS monocytes and serum IgG level of the patients. Stimulation of co-culture of B cells and monocytes with sBAFF drastically enhanced IgG. Moreover, addition of an anti-human sIL-6R antibody to the co-culture significantly inhibited the IgG production.
Conclusions: Our data collectively suggest that the abnormal expression of BR3 on monocytes is responsible for the overproduction of IgG by B cells in pSS patients. IL-6 produced by monocytes stimulated with BAFF may be involved in the activation of B cells to produce IgG.