B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways

Allen, Jessica L.; Fore, Matthew S.; Wooten, Jenna G.; Roehrs, Philip; Bhuiya, Nazmim S.; Hoffert, Todd; Sharf, Andrew; Deal, Allison M.; Armistead, Paul M.; Coghill, James M.; Gabriel, Don A.; Irons, Robert; Essenmacher, Amber; Shea, Thomas C.; Richards, Kristy L.; Cutler, Corey; Ritz, Jérôme; Serody, Jonathan S.; Baldwin, Albert S.; Sarantopoulos, Stefanie

doi:10.1182/blood-2012-06-438911

Cited by 123 publications

(142 citation statements)

References 46 publications

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“…On the other hand, and in contrast to our expectation, we observed lower sjKRECs and cjKRECs from 3 months to 2 years in patients with chronic GVHD (Supplementary Figure 5). This observation does not support the data of Allen et al, 26 which revealed increased numbers of B cells and expression of BAFF (B-cell-activating factor belonging to the TNF family) in patients with chronic GVHD. This discrepancy may be because the patients with chronic GVHD were on more active immunosuppressants compared with those without chronic GVHD.…”

Section: Discussioncontrasting

confidence: 57%

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Nakatani

Imai

Shigeno

et al. 2014

Bone Marrow Transplant

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Hematopoietic cell transplantation (HCT) is used for treatment of hematopoietic diseases. Assessment of T-and B-cell reconstitution after HCT is crucial because poor immune recovery has a major effect on the clinical course. In this study, we retrospectively analyzed T-cell receptor excision circles (TRECs) as well as signal and coding joint kappa-deleting recombination excision circles (sjKRECs and cjKRECs, respectively) as markers of newly produced lymphocytes in 133 patients (56 primary immunodeficient and 77 malignant cases, median (range): 12 (0-62) years old). We analyzed the kinetics of TREC and KREC recovery and determined the factors that contributed to better immune recovery. KRECs became positive earlier than TRECs and increased thereafter. Younger recipient age had a favorable effect on recovery of sjKRECs and cjKRECs. Compared with BM and peripheral blood, our data suggested that cord blood (CB) provided rapid B-cell recovery. CB also provided better B-cell neogenesis in adult HCT recipients. Chronic GVHD was associated with low TRECs, but not increased sjKRECs/cjKRECs. Finally, positive sjKRECs 1 month after HCT were associated with fewer infectious episodes. Monitoring of TRECs and KRECs may serve as a useful tool for assessment of immune reconstitution post HCT.

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Section: Discussioncontrasting

confidence: 57%

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Nakatani

Imai

Shigeno

et al. 2014

Bone Marrow Transplant

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“…The pathophysiology of chronic GVHD includes defects in thymic function/negative selection (44), Tregs (45), clonal deletion (46)(47)(48), and clonal anergy (49,50). In this study, we showed that the PD-1 pathway contributed to the development of chronic GVHD.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death-1 Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Experimental Chronic Graft-versus-Host Disease

Fujiwara

Maeda

Kobayashi

et al. 2014

The Journal of Immunology

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Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2d) donor to BALB/c (H-2d) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti–PD-1, anti–PD-L1, or anti–PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17+IFN-γ+ T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17+IFN-γ+ T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1−/− recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD.

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“…In addition, dysregulation of BAFF levels, especially after depletion of cells consuming BAFF, contribute to pathogenic antibody responses, indicating that pan-depletion of B cells can have deleterious effects on disease progression (128)(129)(130)(131). Long-lived plasma cells lack CD20, the target of rituximab, and account for alloantibody production even after mature B cells that express CD20 are depleted.…”

Section: Role In Renal Transplantationmentioning

confidence: 99%

B Cells, Antibodies, and More

Hoffman¹,

Lakkis

Chalasani

2016

Clinical Journal of the American Society of Nephrology

382

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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B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways

Abstract: Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD).

Cited by 123 publications

References 46 publications

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Programmed Death-1 Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Experimental Chronic Graft-versus-Host Disease

B Cells, Antibodies, and More

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