Background Many autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE), display multiple aberrations in their B cell functions together with a continuous type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs). Type I IFN has a broad range of immunomodulatory effects but less is known about the impact of direct B cell and pDC interactions.
Objectives We asked whether the peripheral blood B cell phenotype is affected by interactions with pDCs and SLE-related immune complexes (IC).
Methods B cells and pDCs were isolated from peripheral blood of healthy individuals and stimulated with immune complexes consisting of IgG from SLE patients and U1snRNP particles (RNA-IC). The cells were cultivated alone or in cocultures for 6 days. Expression of activation markers, cell surface molecules and proliferation were analyzed by flow cytometry and the production of IL-6, IL-10 and IFN-α were analyzed by immunoassays.
Results Both B cells and pDCs displayed an increased expression of activation markers in the cocultures compared to cultures of B cells or pDCs alone. No increased proliferation of the B cells was detected in the RNA-IC-stimulated cocultures. The production of IL-6 was enhanced in the stimulated cocultures compared to the single cultures of B cells or pDCs, in a similar manner as we earlier have described for IFN-α production by pDCs. Cocultivation of B cells with pDCs resulted in a 7-fold increased frequency of CD24hiCD38hi B cells, independently of RNA-IC. This B cell subset is considered to have a regulatory character, however, the IL-10 production was low in the stimulated cultures. Interestingly, we found a highly increased frequency of double negative CD27–IgD– B cells, from 7% among fresh B cells to 37% in the RNA-IC-stimulated cocultures. This was accompanied by a decreased frequency of memory and naïve B cells. In addition, CD95+ expression was induced in a small fraction (1.4%) of the double negative B cells in the RNA-IC-stimulated cultures. We could also confirm a higher frequency of the double negative CD27–IgD– B cells in SLE patients compared to healthy individuals.
Conclusions The pDCs and SLE-related ICs are able to alter the composition and activation of the peripheral blood B cell subsets. Notably, a prominent enrichment of double negative CD27–IgD– B cells, resembling those found in SLE, required presence of both pDCs and SLE related ICs. The functional role of the double negative B cells in SLE is so far unknown, but their presence are reported to correlate with anti-dsDNA autoantibodies and nephritis. Thus, activated pDCs may contribute to the regulation and expansion of potentially pathogenic B cell subpopulations, especially in patients with circulating interferogenic ICs and an ongoing type I IFN production.
Disclosure of Interest None declared
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