Qian, L. et al. Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L. Blood 120, 581

National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China.
Blood (Impact Factor: 10.45). 06/2012; 120(3):581-91. DOI: 10.1182/blood-2011-08-377242
Source: PubMed


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.

Full-text preview

Available from:
  • Source
    • "In addition, CD11clo immature DCs provide critical survival signals to Ag-specific MZ B cells and promote their differentiation into the IgM-secreting plasmablasts19. Our recent study also showed that regulatory DCs can program B cells to differentiate into CD19hiFcγRIIbhi regulatory B cells through IFN-β and CD40L20. Although many studies have been performed to investigate the relationship between DC and B cells, there is still no direct evidence as to whether DCs are capable of regulating the differentiation and functions of B cells during the innate defense against pathogens. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although B cells play important roles in the humoral immune response and the regulation of adaptive immunity, B cell subpopulations with unique phenotypes, particularly those with non-classical immune functions, should be further investigated. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus and Toll-like receptor ligands, we identified an inducible CD11a(hi)FcγRIII(hi) B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of the immune response. This subpopulation of B cells can promote macrophage activation via generating IFN-γ, thereby facilitating the innate immune response against intracellular bacterial infection. As this new subpopulation is of B cell origin and exhibits the phenotypic characteristics of B cells, we designated these cells as IFN-γ-producing innate B cells. Dendritic cells were essential for the inducible generation of these innate B cells from the follicular B cells via CD40L-CD40 ligation. Increased Bruton's tyrosine kinase activation was found to be responsible for the increased activation of non-canonical NF-κB pathway in these innate B cells after CD40 ligation, with the consequent induction of additional IFN-γ production. The identification of this new population of innate B cells may contribute to a better understanding of B cell functions in anti-infection immune responses and immune regulation.Cell Research advance online publication 3 December 2013; doi:10.1038/cr.2013.155.
    Full-text · Article · Dec 2013 · Cell Research
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jan 2013 · Cellular & molecular immunology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Feb 2013 · Cellular & molecular immunology
Show more