ORCID Profile
0000-0002-8394-137X
Current Organisation
University of Tasmania
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Publisher: Informa UK Limited
Date: 03-2011
DOI: 10.1586/ERV.11.6
Abstract: Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010). Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2010
DOI: 10.1038/CDD.2010.43
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.CCELL.2016.05.019
Abstract: E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8 ) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8 ) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.SMIM.2007.12.002
Abstract: Recent advances in the identification of mouse plasma cells have enabled a more detailed assessment of their development and maintenance to be undertaken. Insertion of the gene encoding green fluorescent protein into the Blimp1 locus has allowed measurement of the efficiency and kinetics with which subsets of mature B cells generate antibody-secreting cells (ASCs) after culture with a series of mitogens, with and without co-stimulation. In vivo identification of plasma cells has allowed their phenotype to be defined and changes in their frequency as a result of aging and immunisation to be monitored. This new approach has allowed also a more precise definition of the genetic program activated in plasma cell differentiation. In this review we cover these aspects of plasma cell development with a particular emphasis on the B-cell subsets giving rise to the plasma cells and to their maintenance once formed.
Publisher: Oxford University Press (OUP)
Date: 12-04-2018
Abstract: In recent years multi-parameter flow cytometry has enabled identification of cells at major stages in myeloid development from pluripotent hematopoietic stem cells, through populations with increasingly limited developmental potential (common myeloid progenitors and granulocyte-macrophage progenitors), to terminally differentiated mature cells. Myeloid progenitors are heterogeneous, and the surface markers that define transition states from progenitors to mature cells are poorly characterized. Siglec-F is a surface glycoprotein frequently used in combination with IL-5 receptor alpha (IL5Rα) for the identification of murine eosinophils. Here, we describe a CD11b+ Siglec-F+ IL5Rα− myeloid population in the bone marrow of C57BL/6 mice. The CD11b+ Siglec-F+ IL5Rα− cells are retained in eosinophil deficient PHIL mice, and are not expanded upon overexpression of IL-5, indicating that they are upstream or independent of the eosinophil lineage. We show these cells to have GMP-like developmental potential in vitro and in vivo, and to be transcriptionally distinct from the classically described GMP population. The CD11b+ Siglec-F+ IL5Rα− population expands in the bone marrow of Myb mutant mice, which is potentially due to negative transcriptional regulation of Siglec-F by Myb. Lastly, we show that the role of Siglec-F may be, at least in part, to regulate GMP viability. Identification of a population of GMP-like cells that express Siglec-F are multi-potential and prominent in Myb-mutant mice.
Publisher: Elsevier BV
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 12-2007
DOI: 10.1038/NRI2204
Abstract: B-lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor, and its importance in controlling the terminal differentiation of antibody-secreting cells (ASCs) is well established. However, as we discuss in this Progress article, it has now become evident that the ASC programme consists of a discrete BLIMP1-independent initiation phase, followed by a second step in which BLIMP1 is absolutely required for the differentiation of fully mature ASCs. In addition, an important role for BLIMP1 in maintaining the homeostasis of effector T cells is emerging, suggesting intriguing parallels between the control of effector-cell fates in both B and T cells.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.IMMUNI.2007.04.007
Abstract: Blimp-1 is considered an essential regulator of the terminal differentiation of B cells into antibody-secreting plasma cells. We show here that Rag1-/- mice reconstituted with fetal liver cells homozygous for a DNA-binding-deficient mutant of Prdm1 (the gene encoding Blimp-1) lack a defined plasma-cell compartment, yet show detectable amounts of all immunoglobulin isotypes. In vitro analysis revealed that Blimp-1 is not required for the initiation of antibody secretion but is essential for subsequent high immunoglobulin production. Blimp-1-independent differentiation was blocked at a preplasmablast stage characterized by decreased Pax5 expression and the activation of plasma-cell genes. Analysis of Blimp-1-sufficient differentiation revealed a phase prior to Blimp-1 expression in which several genes normally repressed by Pax5 are re-expressed, suggesting that plasma-cell differentiation is initiated by the inhibition of Pax5 function. Our results indicate that full plasma-cell differentiation but not commitment to the plasma-cell fate requires the expression of functional Blimp-1.
Publisher: The American Association of Immunologists
Date: 04-2007
DOI: 10.4049/JIMMUNOL.178.7.4104
Abstract: The transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein 1) has been described as a “master regulator” of B cell differentiation into Ab-secreting cells (ASCs). Although there is mounting evidence for the importance and necessity of Blimp-1 in plasma cell development, there is uncertainty as to the role it plays in B cell differentiation of B cell subsets and the way in which it may interact with other transcription factors such as Pax5 and Bcl6 during ASC differentiation. Using a mouse expressing GFP under the control of the Blimp-1 regulatory elements (Blimp-1GFP/+), we examined the kinetics of Blimp-1 up-regulation in purified B cell subsets following activation. B1 cells showed the most rapid and pronounced up-regulation of Blimp-1 in response to the mitogens tested, followed by marginal zone B cells and then conventional B2 cells. Interestingly, only B1 cells substantially up-regulated Blimp-1 expression in response to CpG. B1 cells secreted negligible Ig upon isolation but were able to up-regulate Blimp-1 and initiate Ig secretion within 28 h of stimulation. Also of interest, B1 cells have a transcriptional factor profile that is intermediate between a naive B cell and an ASC, indicative of the semiactivated state of B1 cells. Transferred naive Blimp-1GFP/+ B1 and B2 cells both gave rise to ASCs in the bone marrow, suggesting no intrinsic barriers to B1 cell entry into the long-lived ASC compartment.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2013
DOI: 10.1038/NI0813-877C
Publisher: Oxford University Press (OUP)
Date: 05-11-2018
DOI: 10.1093/NAR/GKY1020
Publisher: Oxford University Press (OUP)
Date: 07-11-2015
Abstract: Aicda is a critical component of antibody class-switching in B cells. In this work, we study the impact of TLR4 activation and IL-10 stimulation on Aicda expression in B cells. Through the global analysis of miRNAs in response to TLR4 activation, in combination with IL-10 stimulation, we identified that IL-10 can suppress TLR4-induced miR-155 expression, an effect that resulted in enhanced Aicda expression. Furthermore, when preventing miR-155 control of Aicda expression, by genetic mutation of its target site in the Aicda mRNA, IL-10 could further potentiate Aicda expression. Given that miR-155 expression is lost, and expression levels of both Aicda and IL-10 are high in diseases, such as Burkitt’s lymphoma, our results suggest a stringent and sophisticated control of Aicda by a novel IL-10/miR-155 axis, where the imbalance of IL-10 and/or miR-155 may contribute to disease pathogenesis.
Publisher: Rockefeller University Press
Date: 28-03-2016
DOI: 10.1084/JEM.20151182
Abstract: We examined the role of NFκB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFκB1 (Nfκb1−/−) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity of Nfκb1−/− Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in the Nfκb1−/− mice. Bone marrow chimeric mice revealed that the Fo B cell–intrinsic loss of NFκB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes the differentiation of Fo helper CD4+ T cells and acts in an autocrine manner to reduce antigen receptor and toll-like receptor activation thresholds in a population of proliferating IgM+ Nfκb1−/− Fo B cells. We demonstrate that p50-NFκB1 represses Il-6 transcription in Fo B cells, with the loss of NFκB1 also resulting in the uncontrolled RELA-driven transcription of Il-6. Collectively, our findings identify a previously unrecognized role for NFκB1 in preventing multiorgan autoimmunity through its negative regulation of Il-6 gene expression in Fo B cells.
Publisher: The American Association of Immunologists
Date: 15-06-2010
Abstract: Th cell functional subsets have unique transcriptional programs that form the molecular basis for T cell differentiation and functions. T follicular helper (TFH) cells have emerged as the main providers of T cell help to B cells during the germinal center (GC) reaction, where B cells undergo selection events through competition for Ag and for access to GC T cell-mediated prosurvival and differentiation signals. Because T cell help is one limiting factor for GC B cells, the molecular mechanisms controlling TFH cell abundance and functionality are central to the GC reaction and generation of long-term humoral immunity. Two signaling pathways are absolutely critical for TFH cells: phosphoinositide-3 kinase pathway and the signaling lymphocyte activation molecule-associated protein. In this review, the molecular mechanisms constituting the signaling network in TFH cells will be explored.
Publisher: Wiley
Date: 29-05-2012
DOI: 10.1002/IUB.1046
Abstract: In November 2009, Human Genome Sciences and Glaxo-Smith Kline [HGS (Rockville, Maryland) and GSK, respectively] announced that Belimumab, a neutralizing antibody to the tumour necrosis factor (TNF)-like ligand, B-cell activating factor (BAFF belonging to the TNF family, also named BLyS), met the primary endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE, lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for treatment of SLE patients this was followed in May with approval by the European Medicines Agency for use in the European Union. This is an exciting development as it is the first successful late-stage clinical trial in SLE in over 40 years. In the light of this breakthrough, we review the key data and research outcomes and examine how blocking BAFF in patients with SLE significantly improves clinical outcomes.
Publisher: Wiley
Date: 2019
DOI: 10.1002/CTI2.1083
Publisher: Research Square Platform LLC
Date: 22-03-2021
DOI: 10.21203/RS.3.RS-333716/V1
Abstract: Inflammation is a natural defense mechanism of the body to protect against pathogens. It is induced by immune cells, such as macrophages and neutrophils, which are rapidly recruited to the site of infection, mediating host defense. The processes for eliminating inflammatory cells after pathogen clearance are critical in preventing sustained inflammation which can cause erse pathologies. During chronic inflammation, excessive and uncontrollable activity of the immune system can cause extensive tissue damage. New therapies aimed at preventing this over-activity of the immune system could have major clinical benefit. Here, we investigated the role of the pro-survival Bcl-2 family member A1 in the survival of inflammatory cells under normal and inflammatory conditions using murine models of lung and peritoneal inflammation. Despite the robust upregulation of A1 protein levels in wild-type cells upon induction of inflammation, the survival of inflammatory cells was not impacted in A1 deficient mice compared to wild-type controls. These findings indicate that A1 does not play a major role in immune cell homeostasis during inflammation and therefore does not constitute a therapeutic target for such morbidities.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Oxford University Press (OUP)
Date: 14-05-2018
Abstract: Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL-5 signaling in eosinophil progenitors, many of which were not observed in eosinophils. Eosinophils in Interleukin-5 transgenic mice can be sub ided by Siglec-F expression, and are transcriptionally distinct.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Informa UK Limited
Date: 23-06-2014
DOI: 10.3109/08916934.2014.921810
Abstract: CD19 is a co-stimulatory surface protein expressed exclusively on B cells and serves to reduce the threshold for signalling via the B-cell receptor (BCR). Co-ligation of CD19 with the BCR synergistically enhances mitogen-activated protein (MAP) kinase activity, calcium release and proliferation. We recently found that these parameters were also enhanced in CD19-null primary murine B cells following BCR ligation, suggesting a regulatory role for CD19 in BCR signalling. In this study, we demonstrate that the enhanced BCR signalling in the absence of CD19 was not dependent on the src kinase Lyn, but linked to phosphoinositide 3-kinase (PI3K) activity. Consistent with this, we detect PI3K associated with CD19 outside the lipid raft in resting B cells. Pre-ligation of CD19 to restrict its translocation with the BCR into lipid rafts attenuated BCR-induced PI3K and MAP kinase activation and subsequent B-cell proliferation. Thus, we propose that CD19 can modulate BCR signalling in both a positive and negative manner depending on the receptor/ligand interaction in vivo.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-08-2014
DOI: 10.1126/SCISIGNAL.2005105
Abstract: A nonreceptor tyrosine kinase inhibits cytokine signaling to prevent the persistence of antibody-secreting cells.
Publisher: Springer Science and Business Media LLC
Date: 24-07-2022
Publisher: Springer Science and Business Media LLC
Date: 23-02-2015
DOI: 10.1038/NI.3115
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JAUT.2015.06.001
Abstract: B cell activating factor of the tumor necrosis factor family (BAFF or BLyS) is a critical factor for B cell survival and maturation. BAFF-transgenic (BAFF-Tg) mice develop autoimmunity that resembles systemic lupus erythematosus (SLE) in a T cell-independent but MyD88-dependent manner, implicating toll-like receptor (TLR) signaling. The specific B cell subtypes that make pro-inflammatory autoantibodies in BAFF-Tg mice are TLR-activated innate B cells known as marginal zone (MZ) and B1 B cells. These cells infiltrate the salivary glands and kidneys of diseased BAFF-Tg mice. However, loss of B1a or MZ B cells does not protect BAFF-Tg mice against disease, suggesting that B1b B cells might be the important pathogenic B cell subset. To test this hypothesis, we have generated BAFF-Tg mice that retained follicular B cells, but are deficient in B1a, B1b and MZ B cells, by crossing BAFF-Tg mice to CD19-deficient mice (BTg-CD19(-/-)). The BTg-CD19(-/-) mice did not produce autoantibodies and were protected from splenomegaly, kidney pathology and all signs of autoimmunity. This work suggests that B1b B cells, rather than MZ or B1a B cells, are sufficient and possibly required for the development of autoimmunity. Loss of the majority of innate-like B cells was able to protect BAFF-Tg mice from developing disease, so we can now conclude that autoimmunity induced by excessive BAFF production requires B1b B cells and CD19 signaling.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JAUT.2015.04.007
Abstract: B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2013
DOI: 10.1038/NI.2527
Publisher: Springer Science and Business Media LLC
Date: 19-10-2020
DOI: 10.1038/S41590-020-0799-X
Abstract: A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.IMMUNI.2013.05.019
Abstract: Activation-induced cell death (AICD) plays a critical role in immune homeostasis and tolerance. In T-cell-dependent humoral responses, AICD of B cells is initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B cells. In contrast, T-cell-independent B cell responses involve innate-type B lymphocytes, such as marginal zone (MZ) B cells, and little is known about the mechanisms that control AICD during innate B cell responses to Toll-like receptor (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4 activation in vivo. The transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate expression of both FasL and Fas on MZ B cells and also to repress inhibitors of Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role for TACI and its ligands in the regulation of AICD during T-cell-independent B cell responses.
Publisher: Elsevier BV
Date: 03-2023
Publisher: The American Association of Immunologists
Date: 15-04-2007
DOI: 10.4049/JIMMUNOL.178.8.4764
Abstract: NK cells are important for the clearance of tumors, parasites, and virus-infected cells. Thus, factors that control NK cell numbers and function are critical for the innate immune response. A subset of NK cells express the inhibitory killer cell lectin-like receptor G1 (KLRG1). In this study, we identify that KLRG1 expression is acquired during periods of NK cell ision such as development and homeostatic proliferation. KLRG1+ NK cells are mature in phenotype, and we show for the first time that these cells have a slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. Transfer into lymphopenic recipients indicate that KLRG1− NK cells are precursors of KLRG1+ NK cells and KLRG1 expression accumulates following cell ision. Furthermore, KLRG1+ NK cells represent a significantly greater proportion of NK cells in mice with enhanced NK cell numbers such as Cd45−/− mice. These data indicate that NK cells acquire KLRG1 on their surface during development, and this expression correlates with functional distinctions from other peripheral NK cells in vivo.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-04-2022
Abstract: The human immune system displays substantial variation between in iduals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interin idual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interin idual variation in the immune system.
Publisher: Cold Spring Harbor Laboratory
Date: 06-07-2022
DOI: 10.1101/2022.07.04.22277240
Abstract: Patients with an underlying telomere biology disorder (TBD) have variable clinical presentations and can be challenging to diagnose clinically. A genomic diagnosis for patients presenting with TBD is vital for optimal treatments. Unfortunately, many variants identified during diagnostic testing are variants of uncertain significance (VOUS). This complicates management decisions, delays treatment and risks non-uptake of a potentially curative therapies. Improved application of functional genomic evidence may reduce VOUS classifications. We systematically searched the literature for published functional assays interrogating TBD gene variants. Where possible, established likely benign/benign and likely pathogenic athogenic variants were used to estimate the assay sensitivity, specificity, positive predictive value, negative predictive value and odds of pathogenicity. 3131 articles were screened and 152 met inclusion criteria. Sufficient data to enable a PS3/BS3 recommendation was available for TERT variants only. We recommend PS3 and BS3 can be applied at a moderate and supportive level respectively. PS3/BS3 application was limited by a lack of assay standardisation and limited inclusion of benign variants. Further assay standardisation and assessment of benign variants is required for optimal use of the PS3/BS3 criterion for TBD gene variant classification.
Publisher: American Association for Cancer Research (AACR)
Date: 15-09-2016
DOI: 10.1158/0008-5472.CAN-16-0194
Abstract: New combination immunotherapies are displaying both efficacy and immune-related adverse events (irAE) in humans. However, grade 3/4 irAEs occur in a high proportion, which can lead to discontinuation of treatment and can result in fatalities if not promptly treated. Prolonged T regulatory cell (Treg) depletion in tumor-bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of antitumor responses and severity of irAEs that can occur in ipilimumab/nivolumab-treated patients. In contrast, transient Treg depletion or anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune tolerance threshold and allowing irAEs to be more easily induced following treatment with additional immunomodulatory antibodies. Transient Treg depletion of DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies had a high therapeutic window compared with DT plus anti-CD137. In contrast, DT plus anti-CD137–treated mice developed severe irAEs similar to grade 3/4 clinical symptoms. These irAEs appeared because of an infiltration of activated proliferating effector T cells in the tissues producing IFNγ and TNF however, TNF blockade decreased irAEs severity without impacting on tumor growth. Cancer Res 76(18) 5288–301. ©2016 AACR.
Publisher: Wiley
Date: 08-10-2022
DOI: 10.1111/IMCB.12585
Abstract: The role of B‐cell–activating factor (BAFF) in B‐lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild‐type (WT), BAFF −/− (BAFF deficient), BAFF‐R −/− (BAFF receptor deficient), TACI −/− (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA −/− (B‐cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF‐R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF −/− and BAFF Tg mice produced interferon‐γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2023
No related grants have been discovered for Kirsten Fairfax.