Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Kidney transplantation is the optimal treatment for end-stage renal diseases. Although great improvement has been achieved, immune tolerance is still the Holy Grail that every organ transplant practitioner pursues. The role of B cells in transplantation has long been considered simply to serve as precursors of plasma cells, which produce alloantibodies and induce antibody-mediated rejection. Recent research indicates that a specialized subset of B cells plays an important role in immune regulation, which has been well demonstrated in autoimmune diseases, infections, and cancers. This category of regulatory B cells (Bregs) differs from conventional B cells, and they may help develop a novel immunomodulatory therapeutic strategy to achieve immune tolerance in transplantation. Here, we review the latest evidence regarding phenotypes, functions, and effectors of Bregs and discuss their diverse effects on kidney transplantation.

Related collections

Most cited references 65

Record: found
Abstract: found
Article: not found

Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell–deficient Mice

Susan D. Wolf, Bonnie Dittel, Fridrika Hardardottir … (1996)

Experimental autoimmune encephalomyelitis (EAE) is an animal model for autoimmune central nervous system disease mediated by CD4 T cells. To examine the role of B cells in the induction of EAE, we used B10.PL (I-Au) mice rendered deficient in B cells by deletion of their μ chain transmembrane region (B10.PLμMT). By immunizing B10.PL and B10.PLμMT mice with the NH-terminal myelin basic protein encephalitogenic peptide Ac1-11, we observed no difference in the onset or severity of disease in the absence of mature B cells. There was, however, a greater variation in disease onset, severity, and especially of recovery in the B cell–deficient mice compared to controls. B10.PLμMT mice rarely returned to normal in the absence of B cells. Taken together, our data suggest that B cells do not play a role in the activation of encephalitogenic T cells, but may contribute to the immune modulation of acute EAE. The mechanisms to explain these effects are discussed.

0 comments Cited 177 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans.

Pervinder Sagoo, Esperanza Perucha, Birgit Sawitzki … (2010)

Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.

0 comments Cited 142 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis.

Femina Adatia, Kathryn S. Hebert, H Atkins … (2007)

Although recent animal studies have fuelled growing interest in Ab-independent functions of B cells, relatively little is known about how human B cells and their subsets may contribute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production by normal human B cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B cells exhibit a decreased average production of the down-regulatory cytokine IL-10. Treatment with the approved chemotherapeutic agent mitoxantrone reciprocally modulated B cell proinflammatory and anti-inflammatory cytokines, establishing that the B cell cytokine network can be targeted in vivo. Prospective studies of human B cells reconstituting following in vivo depletion suggested that different B cell subsets produced distinct effector cytokines. We confirmed in normal human B cell subsets that IL-10 is produced almost exclusively by naive B cells while the proinflammatory cytokines lymphotoxin and TNF-alpha are largely produced by memory B cells. These results point to an in vivo switch in the cytokine "program" of human B cells transitioning from the naive pool to the memory pool. We propose a model that ascribes distinct and proactive roles to memory and naive human B cell subsets in the regulation of memory immune responses and in autoimmunity. Our findings are of particular relevance at a time when B cell directed therapies are being applied to clinical trials of several autoimmune diseases.

0 comments Cited 139 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Yingzi Ming: +86 731 88618036 , myz_china@aliyun.com

Cheng Yang: +86 21 64041990 , esuperyc@163.com , yang.cheng1@zs-hospital.sh.cn

Journal

Journal ID (nlm-ta): Cell Death Dis

Journal ID (iso-abbrev): Cell Death Dis

Title: Cell Death & Disease

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-4889

Publication date (Electronic): 25 January 2018

Publication date PMC-release: 25 January 2018

Publication date Collection: February 2018

Volume: 9

Issue: 2

Electronic Location Identifier: 109

Affiliations

[1 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Transplantation Center, The Third Xiangya Hospital, , Central South University, ; Changsha Hunan, 410013 P. R. China

[2 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Department of Urology, Zhongshan Hospital; Shanghai Key Laboratory of Organ Transplantation, , Fudan University, ; Shanghai, 200032 P. R. China

Author information

Bo Peng http://orcid.org/0000-0003-4482-2885

Article

Publisher ID: 152

DOI: 10.1038/s41419-017-0152-y

PMC ID: 5833552

PubMed ID: 29371592

SO-VID: 1d728fe0-bab4-4ae6-8b33-26141f3f29c7

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 September 2017

Date revision received : 16 October 2017

Date accepted : 25 October 2017

Custom metadata

ScienceOpen disciplines: Cell biology

Data availability:

ScienceOpen disciplines: Cell biology

Comments

Comment on this article

scite_

Cited by 39

See all cited by

Most referenced authors 1,207

See all reference authors

- Version 1

Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation

Read this article at

Abstract

Related collections

Stress signalling in stem cells

Most cited references 65

Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell–deficient Mice

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans.

Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 715

Cited by 39

Most referenced authors 1,207