• Background/Purpose: Systemic lupus erythematosus(SLE) was an autoimmune disease characterized by extensive B cell activation and autoantibody production. Human peripheral monocytes could be categorized into three subsets based on differential expression levels of CD14 and CD16: the classical monocytes (CM, CD14++CD16-), the intermediate monocytes (IM, CD14++CD16+) and the nonclassical monocytes (NCM, CD14+CD16++). NCM and IM were collectively addressed as CD16+monocytes. The three subsets had been described to demonstrate diffierent functions in inflammatory process. However, their effects on B cell response in SLE were not well studied.The aim of this study was to determine the frequencies of these subsets and investigate their possible roles in B cell activation and differentiation under SLE condition.

• Methods: The frequencies of monocyte subsets in the peripheral blood of healthy donors (HC) and patients with SLE were determined by flow cytometry (FACS). Monocyte subsets were sorted and co-cultured with CD19+ B cells. B cell were co-cultured for different subsets detection by FACS, while the supernatant were collected for IgG, IgA and IgM detection by enzyme-linked immunosorbent assay (ELISA). The function of monocyte subsets on B cell was defined as the ratio of the effects of monocyte subsets co-cultured with B cell versus the effects of B cell cultured alone. 

• Results: CD16+monocytes were obviously expanded in SLE, while CM were significantly reduced. Compared to HCs, monocyte subsets in patients with SLE demonstrated different phenotypes about HLA-DR, CD163, CD80, CD86, CX3CR1 and CCR5 expression. CD16+monocytes induced CD19+B cells to differentiate into memory B (MB) and plasma B (PB) cells but inhibited the generation of regulatory B (Breg) cell in HC donors. However, both PB response and Breg differentiation induced by CD16+monocytes were exacerbated in patients with SLE. IgG secretion from CD19 positive B cells was increased when cocultured with CD16+monocytes in HCs, which was significantly enhanced when co-cultured with CD16+monocytes in patients with SLE. IgA and IgM responses were differentially regulated by monocyte subsets from SLE and HC, respectively. Compared to CM, CD16+monocytes extensively promoted the expansion of IL-17A- and IL-10- producing B cells, suggesting the preferable role of CD16+monocytes in cytokines secretion from B cells in HCs,. In comparison to HCs, the generation of IL-17A-producing B cells in patients with SLE were significantly elevated in the presence of CD16+monocytes, in which the generation of IL-10 producing B cells were obviously attenuated .

• Conclusion: CD16+monocytes was enriched and shared different cell-surface marker profiles in SLE. These cells played a predominant role in orchestrating B cell activation and differentiation in SLE.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd16monocytes-are-enriched-and-functionally-exacerbated-in-driving-b-cell-activation-under-systemic-lupus-erythematosus-condition/