The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

Xu, Haiyan; He, Xiaozhou; Liu, Qing; Chen, Yingdi; Zhu, Yueyong; Shi, Daren; Zhang, Xueguang

doi:10.1038/cmi.2008.58

Cited by 12 publications

(13 citation statements)

References 28 publications

(28 reference statements)

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“…The inflammatory cytokine IL6 supports long-lived plasma cell survival in vitro and it is increased in the serum of patients with SLE 14,50 and in monocytes from SLE patients. 51 Increased expression of the prosurvival cytokine BAFF has also been associated with abnormal renal function, 52 and in patients with active SLE, BAFF is expressed by CD4 and CD8 T cells but also by plasma cells from both the bone marrow and kidneys, 31,53 raising the possibility that autocrine secretion of BAFF might promote PC survival in lupus kidneys. Further characterization of the factors that regulate survival of these cells will be crucial to devise methods for their control.…”

Section: Discussionmentioning

confidence: 99%

Local Renal Autoantibody Production in Lupus Nephritis

Espéli¹,

Bökers²,

Giannico³

et al. 2011

Journal of the American Society of Nephrology

131

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Autoantibodies are central to the pathogenesis of several autoimmune diseases including systemic lupus erythematosus. Plasma cells secrete these autoantibodies, but the anatomical sites of these cells are not well defined. Here, we found that although dsDNA-specific plasma cells in NZB/W mice were present in spleen and bone marrow, a large number were in the kidneys and their number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells only in mice with nephritis, where they located mainly to the tubulointerstitium of the cortex and outer medulla. These cells had the phenotypic characteristics of fully differentiated plasma cells and, similar to long-lived bone marrow plasma cells, they were not in cell cycle. In patients with lupus nephritis, plasma cells were often present in the medulla in those with the most severe disease, especially combined proliferative and membranous lupus nephritis. The identification of the kidney as a major site of autoreactive plasma cells has implications for our understanding of the pathogenesis of lupus nephritis and for strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.

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Section: Discussionmentioning

confidence: 99%

Local Renal Autoantibody Production in Lupus Nephritis

Espéli¹,

Bökers²,

Giannico³

et al. 2011

Journal of the American Society of Nephrology

131

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“…BAFF/BLyS and APRIL blockade prevents B cell maturation, differentiation, and survival [86]. Xu et al found a gradual increase in levels of BAFF over time in kidney transplant recipients as well as higher levels of BAFF expression on CD3 T cell in patients with poorer graft function [87]. BAFF has been shown to influence class switching of immunglobulins, enhance survival and effector function of plasmablasts [88–90] as well as memory B cell differentiation into Ig-secreting cells in a T cell dependent manner, while opposite results were seen with respect to T cell independent responses [91].…”

Section: The Effects Of Immunosuppressants On B- Cellsmentioning

confidence: 99%

The role of B cells in solid organ transplantation

Kwun

Bulut

Kim

et al. 2012

Seminars in Immunology

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The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

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“…BAFF and APRIL are members of the TNF family and contribute to survival of bone marrow plasma cells. Recent studies have shown up-regulation of BAFF in peripheral blood of patients with AMR (30–31). CD138+ plasma cells could still be associated with AMR that was missed in our study due to small sample size and inability to examine DSA, BAFF, or APRIL.…”

Section: Discussionmentioning

confidence: 99%

Significance of Intragraft CD138+ Lymphocytes and p-S6RP in Pediatric Kidney Transplant Biopsies

et al. 2010

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Background-We have previously shown that intragraft CD20+ B cells are associated with acute cellular rejection (ACR) and and allograft loss. Phosphorylation of S6 ribosomal protein, a downstream target of the PI3K/Akt/mTor pathway, promotes growth and proliferation of cells and could identify metabolically active cells such as alloantibody secreting plasma cells. Since CD20+ lymphocytes can differentiate into CD138+ plasma cells, we aimed to identify functionally active

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The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

Cited by 12 publications

References 28 publications

Local Renal Autoantibody Production in Lupus Nephritis

Local Renal Autoantibody Production in Lupus Nephritis

The role of B cells in solid organ transplantation

Significance of Intragraft CD138+ Lymphocytes and p-S6RP in Pediatric Kidney Transplant Biopsies

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