Murine Islet Allograft Tolerance Upon Blockade of the B-Lymphocyte Stimulator, BLyS/BAFF

Parsons, Ronald F.; Yu, Ming; Vivek, Kumar; Zekavat, Ghazal; Rostami, Susan; Ziaie, A.; Luo, Yanping; Koeberlein, Brigitte; Redfield, Robert; Ward, Christopher; Migone, Thi Sau; Cancro, Michael P.; Naji, Ali; Noorchashm, Hooman

doi:10.1097/tp.0b013e318246621d

Cited by 27 publications

(17 citation statements)

References 45 publications

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“…The B-cell activating factor is involved not only in survival but also in maturation of B cells [8], and it was suggested as a candidate biomarker of humoral rejection in animal models [9]. Nevertheless, recently in kidney transplant recipients no correlation between B-cell activating factor levels and antiehuman leukocyte antigen (HLA) antibody development was described [10], whereas an increased proportion of activated naïve B cells in kidney transplant recipients who develop anti-HLA antibodies was confirmed [10].…”

Section: Discussionmentioning

confidence: 96%

Frequencies of Circulating B-Cell Subpopulations Before Kidney Transplantation Identify Patients at Risk of Acute Rejection

Segundo

Rodrigo

Kislikova

et al. 2015

Transplantation Proceedings

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Section: Discussionmentioning

confidence: 96%

Frequencies of Circulating B-Cell Subpopulations Before Kidney Transplantation Identify Patients at Risk of Acute Rejection

Segundo

Rodrigo

Kislikova

et al. 2015

Transplantation Proceedings

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“…Post hoc analysis of the trial data demonstrated improvement in renal flare rates and reduction in proteinuria with anti-BAFF, with greatest benefit in those with high disease activity, suggesting efficacy in lupus nephritis, while serologic memory to past vaccine immunizations was preserved (163)(164)(165). It remains to be examined whether the beneficial effects of anti-BAFF in lupus are due to resetting aberrant checkpoints of peripheral B-cell tolerance eliminating autoreactive clones and/or attenuating T-cell activation by blocking costimulatory functions of BAFF (65,166).…”

Section: Role In Gnmentioning

confidence: 99%

B Cells, Antibodies, and More

Hoffman¹,

Lakkis

Chalasani

2016

Clinical Journal of the American Society of Nephrology

370

268

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B cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell-targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell-targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation.

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“…However, these results were obtained in a globally immune cell depleted context ( scid mice). Results currently in press for mice illustrate the potential effectiveness of B cell depletion at transplant followed by periodic, gradually decreasing doses of anti-BLyS [115]. In this work, fully allogeneic transplanted pancreatic islets were maintained for more than 6 months after cessation of anti-BLyS treatment; moreover, subsequent new transplants of the same MHC haplotype were accepted and maintained.…”

Section: Resolve Revise and Relax: The 3 Rs Of Repertoire Adjustmentioning

confidence: 82%

Resolve, revise, and relax: The 3 Rs of B cell repertoire adjustment

Scholz

Cancro

2012

Immunology Letters

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Competition for limited, cell extrinsic survival factors is a general feature of peripheral selection checkpoints involved in B lymphocyte maturation and activation. Perhaps the best-characterized example involves BLyS (B lymphocyte stimulator), which modulates the size and composition of mature naïve B cell pools, but evidence for analogous competitive checkpoints is emerging for both germinal center B cells and plasma cells. Here we discuss how deliberate alteration of BLyS levels might be used to manipulate B cell repertoire selection in order to restore self-tolerance in autoimmunity, remodel the repertoire to accommodate neo-self antigens introduced through transplantation and gene therapy, or expand repertoire diversity to reveal novel, therapeutically useful specificities.

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Murine Islet Allograft Tolerance Upon Blockade of the B-Lymphocyte Stimulator, BLyS/BAFF

Abstract: In vivo BLyS neutralization effectively induces humoral tolerance and promotes long-term islet allograft survival in mice. Therefore, B-lymphocyte-directed immunotherapy targeting the homeostatic regulator, BLyS, may be effective in promoting transplantation tolerance.

Cited by 27 publications

References 45 publications

Frequencies of Circulating B-Cell Subpopulations Before Kidney Transplantation Identify Patients at Risk of Acute Rejection

Frequencies of Circulating B-Cell Subpopulations Before Kidney Transplantation Identify Patients at Risk of Acute Rejection

B Cells, Antibodies, and More

Resolve, revise, and relax: The 3 Rs of B cell repertoire adjustment

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