Background/Purpose: BAFF (B cell stimulation factor belonging to TNF family) is a cytokine which is mainly produced by monocytes, dendritic cells and T cells. We have been investigating the possible involvement of BAFF in the pathogenesis of primary Sjögren’s syndrome (pSS) because BAFF plays a pivotal role in the proliferation, differentiation and survival of B cells. 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 (BAFF-R) was significantly elevated in pSS monocytes compared to that of normal monocytes. These data collectively suggest that the elevated expression of BAFF-R on monocytes 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. On the other hand, it is well known that pSS is often accompanied by hypergammaglobulinemia (HγG). However, the molecular and cellular mechanism underlying HγG is unknown. In the present study, we focused on this abnormality and investigated the possible involvement of monocytes producing IL-6 in the development of HγG.

Methods: Peripheral monocytes were cultured with or without peripheral B cells and stimulated with soluble BAFF (sBAFF) in vitro. IL-6 production by monocytes and IgG production by B cells were measured by ELISA. FACS analysis of whole blood samples was employed to analyze the expression of BAFF-R.

Results: The serum level of IgG and the proportion of BAFF-R positive monocytes (BR⁺/CD14⁺) were elevated in pSS patients as compared to those in normal individuals. Remarkably, the BR⁺/CD14⁺ ratio was positively and significantly correlated with the serum IgG level. In addition, pSS monocytes produced a significantly higher amount of IL-6 than normal monocytes upon stimulation with sBAFF in vitro, and the BR⁺/CD14⁺ ratio was positively and significantly correlated with the amount of IL-6 produced by pSS monocytes. Stimulation of co-culture of B cells and monocytes with sBAFF drastically enhanced IgG production by B cells in vitro, whereas the stimulation showed only marginal effects on IgG production when B cells were cultured in the absence of monocytes.

Conclusion: The data in the present study collectively suggest that the abnormal expression of BAFF-R on monocytes is responsible for the overproduction of IgG by B cells in pSS patients. IL-6 produced by monocytes may be involved in the differentiation of B cells to produce IgG. We presume that aberrations of monocytes may underlie the development of hypergammaglobulinemia in pSS patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-expression-of-baff-receptor-on-monocytes-is-a-contributory-factor-of-hypergammaglobulinemia-in-patients-with-primary-sjogrens-syndrome/