Cytokine-producing B lymphocytes—key regulators of immunity

Lund, Frances E.

doi:10.1016/j.coi.2008.03.003

Cited by 479 publications

(415 citation statements)

References 53 publications

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“…B cells can secrete a variety of cytokines (73,74), among which IL-10 is of particular interest because it is closely associated with the regulatory function of B cells. There is convincing evidence in animal models that IL-10-producing B cells can suppress autoimmune and inflammatory processes (75)(76)(77).…”

Section: Discussionmentioning

confidence: 99%

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Mannoor

Matejuk

et al. 2012

The Journal of Immunology

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Natural autoantibodies (NAA) and their associated B cells constitute a substantial proportion of the normal Ab and B cell repertoire. They often have weak reactivity toward a variety of self-Ags such as DNA, nucleoproteins, and phospholipids. It remains controversial whether NAA contribute to or protect from autoimmune diseases. Using site-directed transgenic (sd-tg) mice expressing a prototypic NAA, we investigated the effect of NAA and NAA-producing B cells in disease development in the autoimmune-prone MRL/MpJ-Faslpr (MRL-lpr) mice. We found that the expression of NAA in MRL-lpr mice prevented proteinuria and reduced kidney immune complex formation. The mice had significantly improved survival. Administration of the IgM NAA to MRL-lpr mice also delayed the onset of nephritis. The sd-tg MRL-lpr mice had decreased levels of anti-dsDNA Abs, anti-Hep2 nuclear Abs, and anti-Sm/ribonucleoprotein Abs. There is a shift in the IgG subclass profile from IgG2a and IgG3 to IgG1 in the sd-tg MRL-lpr mice. The CD4+ T cells from the sd-tg MRL-lpr mice had increased expression of the negative costimulatory molecule CTLA-4 and increased production of IL-10 as compared with those from the wild-type mice. Furthermore, the NAA B cells produced large amounts of IL-10 upon TLR stimulation. These results indicate that NAA and NAA-producing B cells play an important role in protection from lupus nephritis and suggest that the NAA B cells may have an immune regulatory function via the provision of IL-10.

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Section: Discussionmentioning

confidence: 99%

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Mannoor

Matejuk

et al. 2012

The Journal of Immunology

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“…First, it is important to note that patients in the second study were subjected to chemotherapy (which can profoundly affect the numbers and functionality of immune cell subsets), while those in the first study were not. Second, while CD20 is present on the surface of all mature B cells [33][34][35], and CD19 is predominantly expressed on B cells [36] [39,40]. B cells are capable of influencing T cell memory, survival, and proliferation [41,42], as well as presenting antigen to both CD4 + and CD8 + T cells [38,43] …”

Section: Intraepithelial Presence Of B Cells Was Positively Correlamentioning

confidence: 99%

Antigen-Presenting Cell (APC) Subsets in Ovarian Cancer

Wilke

Kryczek

Zou

2011

International Reviews of Immunology

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“…These findings suggest that cell extrinsic factors play an important role in augmentation and perpetuation of the autoimmune process. There are several ways in which activated congenic self-reactive B cells could have an impact upon surrounding cells: (i) as an APC, by presenting autoantigens to T cells and driving their activation; (ii) by secreting autoantibodies that form immune complexes (ICs) and drive further B-cell and APC activation; and/or (iii) through the exogenous secretion of cytokines, including, IL-2, IL-4, IL-6, IL-12, TNF-a, and IFN-g (with the latter half representing proinflammatory cytokines) [8,32]. Of these potential mechanisms, the latter appears the most likely, because abnormal T-cell activation and autoantibody production was absent in B6.NZBc13 MC mice.…”

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confidence: 99%

An intrinsic B‐cell defect supports autoimmunity in New Zealand black chromosome 13 congenic mice

et al. 2010

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Introgression of a New Zealand Black (NZB) chromosome 13 interval onto a C57BL/6 (B6) background (B6.NZBc13) is sufficient to produce many hallmarks of lupus, including hightitre anti-chromatin antibody production, abnormal B-and T-cell activation, and renal disease. In this study we sought to characterize the immune defects leading to these abnormalities. By generating hematopoietic chimeras and BCR transgenic mice, we show that the congenic autoimmune phenotype can be transferred by BM cells and requires the presence of autoreactive B cells. Using the hen egg white lysozyme immunoglobulin transgenic mouse model, we demonstrate that B-cell anergy, deletion, and receptor editing are intact. Nevertheless, congenic B cells exhibit altered peripheral B-cell selection, as demonstrated by enhanced survival and activation of endogenous B cells with autoreactivity to chromatin and Sm/ribonucleoprotein. Given the autoantibody specificities to nuclear antigens, TLR signalling was assessed. B6.NZBc13 B cells were hyper-responsive to poly(I:C), a TLR3 ligand, demonstrating enhanced proliferation and survival as compared to B6 B cells. Our findings indicate the presence of an intrinsic B-cell defect on NZB chromosome 13 that results in hyper-responsiveness to a dsRNA analogue and implicates its potential supporting role in the generation of autoimmunity in B6.NZBc13 mice. Keywords: Autoimmunity . B cells . TLRs Supporting Information available online IntroductionSystemic lupus erythematosus is a chronic autoimmune disorder characterized by the production of antibodies directed against nuclear antigens (ANAs). Similar to human lupus, the New Zealand Black (NZB) mouse produces antibodies directed against nuclear antigens, develops Coomb's positive hemolytic anaemia, and exhibits a number of phenotypic and functional B-cell abnormalities (reviewed in [1]). Although glomerulonephritis is mild in these mice, severe nephritis develops when the NZB background is crossed onto a permissive MHC haplotype (H-2 bm12 ), indicating that this mouse possesses a full complement of non-MHC lupus susceptibility genes [2].Generation of congenic mice, by introgression of homozygous chromosomal intervals from the NZB mouse strain onto a normal mouse C57BL/6 (B6) background, has been a particularly useful technique for characterizing susceptibility loci and their role in disease genesis [3]. In our mapping study of (B6 Â NZB) F 2 mice, we identified a locus on NZB chromosome (c) 13 that was linked to increased B-cell activation and abnormal IgM production [4]. To further characterize this locus, we generated congenic mice with an NZB c13 interval (denoted B6.NZBc13). B6.NZBc13 mice spontaneously developed autoimmunity characterized by hightitre IgM and IgG anti-chromatin antibody production, increased 527T-cell activation, expansion of DCs, and the development of mild glomerulonephritis [5]. Moreover, as predicted from our mapping study, B6.NZBc13 mice closely recapitulated the abnormal polyclonal B-cell activation and B-cell subset distribution...

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Cytokine-producing B lymphocytes—key regulators of immunity

Cited by 479 publications

References 53 publications

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Antigen-Presenting Cell (APC) Subsets in Ovarian Cancer

An intrinsic B‐cell defect supports autoimmunity in New Zealand black chromosome 13 congenic mice

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