Plasmacytoid Dendritic Cells Induce Plasma Cell Differentiation through Type I Interferon and Interleukin 6

Abstract

Dendritic cells (DCs) initiate and control immune responses. Plasmacytoid DCs (pDCs) represent a unique DC subset able to promptly release large amounts of type I interferon (IFN-alphabeta) upon viral encounter. Here we report that depletion of pDCs from human blood mononuclear cells abrogates the secretion of specific and polyclonal IgGs in response to influenza virus. Furthermore, purified pDCs triggered with virus induce CD40-activated B cells to differentiate into plasma cells. Two pDC cytokines act sequentially, with IFN-alphabeta generating non-Ig-secreting plasma blasts and IL-6 inducing their differentiation into Ig-secreting plasma cells. These plasma cells display the high levels of CD38 found on tissue plasma cells. Thus, pDCs are critical for the generation of plasma cells and antibody responses.

The role of nitric oxide in abnormal T cell signal transduction in systemic lupus erythematosus

“…Most patents with SLE have increased IFN serum levels and majority of active SLE patients were reported to have increased transcription of IFN regulated genes (IFN biosigniture) [59]. INF-α appears to be the main factor driving unabated DC differentiation/activation in SLE [60]. In SLE, the plasmocytoid dendritic cells release large amounts of IFN, which induces DC maturation.…”

The type I interferon system in systemic lupus erythematosus

“…Type I IFNs also markedly stimulate development of cytotoxic T cells, in part because of an increased cross-presenting function of dendritic cells (30) and prevention of apoptosis of activated T cells (31,32). Furthermore, the type I IFNs decrease the threshold for activation of B cells via the B cell receptor (BCR) and enhance differentiation, antibody production, and immunoglobulin isotype class switching (33)(34)(35). Therefore, the type I IFNs serve as a bridge between innate and adaptive immunity and can be viewed as stress hormones in the immune system, signaling danger and contributing to its activation.…”

A macrophage marker, siglec‐1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll‐like receptor agonists

“…In these studies, sera from SLE patients were shown to induce normal monocytes to differentiate into DCs in a type I IFN-dependent manner. Type I IFNs are also known to support critical points in the maturation of B cells into plasma cells, which represents another potential role in the pathogenesis of SLE (14). The occasional observation of the development of either SLE or SSc during the course of type I IFN therapy (15)(16)(17) suggests that this mediator might contribute to the pathogenesis of both of these diseases.…”