Regulatory dendritic cells program B cells to differentiate into CD19hiFc IIbhi regulatory B cells through IFN- and CD40L
ABSTRACT Regulatory dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Our previous studies demonstrate that splenic stroma can drive mature DCs to proliferate and further differentiate into a unique subset of CD11b(hi)Ia(low) regulatory DCs, which could inhibit T-cell response, program generation of immunosuppressive memory CD4 T cells. However, the effect of regulatory DCs on B-cell function remains unclear. Here, we report that regulatory DCs can induce splenic B cells to differentiate into a distinct subtype of IL-10-producing regulatory B cells with unique phenotype CD19(hi)FcγIIb(hi). CD19(hi)FcγIIb(hi) B cells inhibit CD4 T-cell response via IL-10. CD19(hi)FcγIIb(hi) B cells have enhanced phagocytic capacity compared with conventional CD19(+) B cells, and FcγRIIb mediates the uptake of immune complex by CD19(hi)FcγIIb(hi) B cells. We found that regulatory DC-derived IFN-β and CD40 ligand are responsible for the differentiation of CD19(hi)FcγIIb(hi) B cells. Furthermore, an in vivo counterpart of CD19(hi)FcγIIb(hi) B cells in the spleen and lymph nodes with similar phenotype and regulatory function has been identified. Our results demonstrate a new manner for regulatory DCs to down-regulate immune response by, at least partially, programming B cells into regulatory B cells.
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ABSTRACT: Recent immune data on vitamin D3 deficiency help to more clearly understand chronic fatiguing illnesses, such as autoimmune disorders, cancer and chronic fatigue syndrome (CFS). The vitamin D3 pathway is activated by stress and requires sufficient stores of precursor 25-hydroxyvitamin D3 for proper cell and immune functions. In vitamin D3 deficiency, secretion of the antimicrobial peptide cathelicidin is reduced, leading to impaired auto/xenophagy. As a result, phagocytosis, cytotoxicity, antigen processing and antigen presentation become dysregulated. In addition, vitamin D3 deficiency affects T- and B-lymphocyte activation, as well as quantity, maturation and function of regulatory natural killer T-cells and their counterparts in the gut, i.e. T-cell receptor-αβ, cluster of differentiation-8αα-positive intraepithelial lymphocytes. Consequently, innate and adaptive immunity become de-regulated, with microbial effects contributing further to this. Persistent infections, chronic inflammation and fatigue follow. Vitamin D3 substitution in such conditions may help to prevent or to ameliorate such chronic conditions, even in patients with cancer.In vivo (Athens, Greece) 28(1):133-45. · 1.15 Impact Factor
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ABSTRACT: B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4(+) T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B cells are defined as regulatory B (Breg) cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases.Cellular & Molecular Immunology advance online publication, 7 January 2013; doi:10.1038/cmi.2012.60.Cellular & molecular immunology 01/2013; DOI:10.1038/cmi.2012.60 · 4.19 Impact Factor
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ABSTRACT: Innate-like B cells (ILBs) are heterogeneous populations of unconventional B cells with innate sensing and responding properties. ILBs in mice are composed of B1 cells, marginal zone (MZ) B cells and other related B cells. ILBs maintain natural IgM levels at steady state, and after innate activation, they can rapidly acquire immune regulatory activities through the secretion of natural IgM and IL-10. Thus, ILBs constitute an important source of IL-10-producing regulatory B cells (Bregs), which have been shown to play critical roles in autoimmunity, inflammation and infection. The present review highlights the latest advances in the field of ILBs and focuses on their regulatory functions. Understanding the regulatory activities of ILBs and their underlying mechanisms could open new avenues in manipulating their functions in inflammatory, infectious and other relevant diseases.Cellular & Molecular Immunology advance online publication, 11 February 2013; doi:10.1038/cmi.2012.63.Cellular & molecular immunology 02/2013; 10(2). DOI:10.1038/cmi.2012.63 · 4.19 Impact Factor