Maturation and function of human dendritic cells are regulated by B lymphocytes

Abstract

IntroductionDendritic cells (DCs) are potent professional APCs that sensitize T cells to switch on appropriate immune responses to Ag danger signals. For this to occur, they take up Ags in peripheral tissues and transport them to lymphoid organs, where they interact with T cells to prime a specific response. 1 This property of DCs implies particular characteristics, including high expression of HLA class II molecules for efficient Ag presentation, high expression of CD80 and CD86 costimulatory molecules, and production of T-cell activating cytokines, such as IL-12, to trigger differentiation of T cells into efficient Th1 effector cells. 2 To acquire these characteristics, DC precursors differentiate into immature (iDC) and then to mature DCs (mDCs) 3 as a result of activation mediated by GM-CSF and IL-4 and by TLR-activating products such as lipopolysaccharides (LPS). However, the functional properties of DCs vary depending on the stage of maturation. Thus, mDCs stimulate T-cell immunity, whereas iDCs favor T-cell tolerance rather than immunity. 4 Furthermore, autoimmune diseases such as systemic lupus erythematosus (SLE) might result from break-in peripheral tolerance because of the activation of DCs. 5 If so, the control of the maturation and function of DCs should provide important tools to modulate aberrant autoimmune and inflammatory responses. 6,7 B cells were first recognized as immune cells committed to Ab production, ie, defined as effector cells of the humoral immune response. However, the authors of numerous studies have since discovered that B cells are regulators of immunity. 8 They have the ability to synthesize cytokines, 9 to act as APCs for T cells, 10 and to govern the architecture of secondary lymphoid organs by encouraging the development of DCs. 11 Moreover, murine models of autoimmune and inflammatory diseases have suggested that B cells also may regulate pathologic processes.After the release of one or several mediators and/or direct cell-to-cell contacts, B cells can modulate DC functions and consequently immune responses. Thus, in mice with lupus, autoreactive B cells contribute to the severity of the disorder once activated through their TLR9 but also exert a negative role on DC function if they secrete considerable amount of In the MT mouse model of arthritis, B cells are lacking and hence, DCs produce high quantities of proinflammatory IL-12p70 and do not secrete IL-4, compared with wild-type mice. This DC-mediated exacerbation of the inflammatory response is caused by the absence of IL-10 high -secreting B cells. 13 The results of these experiments suggest that B cells have the ability to regulate DC functions and thereby to control the induction of immune responses. However, much evidence indicates that B cells can also modulate the immune reactions by controlling T-cell responses. For example, in the TCR␣ Ϫ/Ϫ Ig Ϫ/Ϫ murine model of inflammatory bowel disease, 14 the development of spontaneous chronic colitis is downregulated by the transfer of B cells from TCR␣ Ϫ/Ϫ mice. B cells i...

B Cells, Antibodies, and More

“…In addition to B cells, some plasmablasts (IgM 1 CD138 1 ) exert regulatory functions via production of the cytokine IL-35 (97). Via IL-10 or IL-35, Bregs modulate innate cells, such as DCs, macrophages, or natural killer cells (e.g., decreased IL-6 and IL-12), decrease inflammatory T-cell cytokines, and increase regulatory Tregs, curtailing the ongoing immune response (95,(97)(98)(99)(100)(101). Bregs have also been identified in humans, specifically in the CD24 high CD38 high transitional and CD24 high CD27 1 memory B-cell subsets, and their numbers correlate with better renal transplant outcomes (102)(103)(104).…”

Insulin-like Growth Factor-2 Enhances Functions of Antigen (Ag)-specific Regulatory B Cells

“…3P), which were in parallel to the frequency of IL-10 ϩ OVAsBCs in Fig. 3 Based on published data that IL-10-expressing B cells also express other cytokines (21,22), we further analyzed the phenotypes of IL-10 ϩ OVAsBCs. Positive staining of CD5, CD38, CD1d, TIM1, CD23, and CD27 was observed in 56 -78% of OVAsBCs.…”

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified Aromatic-Turmerone (AR)

“…Dendritic cells immunogenicity, and from a better understanding of the cell dynamics whereby immune responses are orchestrated. [29][30][31][32][33][34] Here, we discuss these new insights together with an overview of the DC-based clinical studies performed to date. Therefore, in this study, we used AR to promote the maturation process of DCs from antigen-capturing cells into antigen-presenting cells.…”