IL-21: An Executor of B Cell Fate

Konforte, Danijela; Simard, Nathalie; Paige, Christopher J.

doi:10.4049/jimmunol.0803009

Cited by 132 publications

(112 citation statements)

References 72 publications

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“…IL-21 is a key regulator of the differentiation of activated B lymphocytes into plasma and promotes IgM, IgG and IgA production [23,24,40]. We found that the levels of serum IL-21 were significantly higher in the RA patients than that in the HC.…”

Section: Tfh and Cd95mentioning

confidence: 53%

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High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

Wang

Shan

Jiang

et al. 2013

Clinical and Experimental Immunology

170

166

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Section: Tfh and Cd95mentioning

confidence: 53%

“…2b). Given that Tfh cells can secrete IL-21, which has been shown to regulate B cell differentiation and proliferation [23][24][25], we examined the concentrations of serum IL-21 in those patients and HC by ELISA (Fig. 2c).…”

Section: Cxcr5mentioning

confidence: 99%

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

Wang

Shan

Jiang

et al. 2013

Clinical and Experimental Immunology

170

166

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“…Moreover, Il-21 also inhibits the development of Treg, which can suppress autoimmune responses in NMO and MS 17,18 . Most importantly, Il-21 is recognized as "An executor of B Cell Fate" 19 : Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, Il-21 can induce B cell proliferation, differentiation into Ig-producing plasma cells, or apoptosis. Alone and in combination with Th cell-derived cytokines Il-21 can regulate class switch recombination to IgG, IgA, or Ige isotypes, indicating its important role in shaping the effector function of B cells.…”

mentioning

confidence: 99%

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Zhong²,

Wang³

et al. 2012

Can. J. Neurol. Sci.

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Neuromyelitis optica (NMO) and Multiple sclerosis (MS) are two typical inflammatory demyelinating diseases of the central nervous system (CNS) with complex pathogenesis, and they share many similarities. Neuromyelitis optica was considered an optic-spinal form of MS until specific antibodies (NMO-IgG) were suggested to be a biomarker of NMO, distinguishing it from conventional MS 1 . T cells have emerged as a key player in the pathogenesis of MS 2 . We also found increased levels of CD4 + T cells in NMO patients 3 . Simultaneously, B cells are believed to play an important role in the pathogenesis of these diseases. A role of B cells in MS pathogenesis has been suggested by the presence of oligoclonal immunoglobulin bands (OCBs) in cerebrospinal fluid (CSF) 4,5 . In addition, NMO-IgG is compelling evidence for B cells involvement in NMO pathogenesis 6 . Moreover, therapies which eliminate antibodies ABSTRACT: Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. Il-21/Il-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum Il-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) Il-21 in MS and NMO patients still remain unknown. Object: To detect the CSF concentration of Il-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. Methods: CSF Il-21 was detected by an enzyme-linked immunosorbent assay (elISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). Results: CSF concentration of the Il-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between Il-21 and complement in NMO cohort (p=0.023) and high Il-21 levels in autoantibodypositive subgroup (p=0.027). Conclusions: The concentration of CSF Il-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO. RÉSUMÉ: Les niveaux d'IL-21 du liquide céphalo-rachidien dans

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“…If possible, we will detect Th17 cells at the late stage of X-GVHD in the future. The impact of IL-21 on human B-cell responsiveness was addressed in vitro, and all of the experiments were carried out, in which human B cells were isolated and stimulated with IL-21 in combination with anti-CD40 and/or anti-IgM, which mimic the BCR-antigen and B cell-T cell interaction (Ettinger et al, 2008;Konforte et al, 2009). Notably, IL-21 was found to induce proliferation and differentiation of human B cells isolated from PBMCs and spleen (Ettinger et al, 2005;Good et al, 2006).…”

Section: Protein Cellmentioning

confidence: 99%

IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation

Tan

Xing

et al. 2013

Protein Cell

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Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell trans-plantation. An animal model, xenogeneic GVHD (X-GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/cRag2 −/− IL-2Rγc −/− (BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19 + B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19 + CD38 high plasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the fi rst to fi nd in vivo expansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our fi ndings show evidence of the involvement of B cells in X-GVHD and may have implications in the treatment of the disease.

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IL-21: An Executor of B Cell Fate

Cited by 132 publications

References 72 publications

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation

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