Regulatory and Effector B Cells: A New Path Toward Biomarkers and Therapeutic Targets to Improve Transplant Outcomes?

Aravind Cherukuri; Qing Ding; Akhil Sharma; Kanishka Mohib; David M Rothstein

doi:10.1016/j.cll.2018.10.011

Regulatory and Effector B Cells: A New Path Toward Biomarkers and Therapeutic Targets to Improve Transplant Outcomes?

Clin Lab Med. 2019 Mar;39(1):15-29. doi: 10.1016/j.cll.2018.10.011. Epub 2018 Dec 18.

Authors

Aravind Cherukuri¹, Qing Ding², Akhil Sharma¹, Kanishka Mohib², David M Rothstein³

Affiliations

¹ Section of Nephrology, Department of Medicine, University of Pittsburgh, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1545 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
² Department of Surgery, University of Pittsburgh, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, W1545 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
³ Departments of Surgery, Medicine and Immunology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, W1545 Biomedical Science Tower, Pittsburgh, PA 15261, USA. Electronic address: rothsteindm@upmc.edu.

Abstract

B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines. Their summed activity dictates the influence of B cells on the alloimmune response. We review the evidence for regulatory B cells and effector B cells in mice and humans, discuss current limitations in their phenotypic identification, and discuss regulatory B cells as a signature for clinical renal allograft tolerance and predictive markers for allograft outcomes. We discuss the effects of therapeutic agents on regulatory B cells and potential approaches to augment their numbers as a therapeutic tool.

Keywords: Biomarker; Effector B cells; Human; IL-10; Mouse; Regulatory B cells; TNF-α; Transplant tolerance.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
B-Lymphocyte Subsets / metabolism
B-Lymphocyte Subsets / physiology*
B-Lymphocytes, Regulatory / metabolism
B-Lymphocytes, Regulatory / physiology*
Biomarkers / metabolism
Humans
Mice
Transplantation Tolerance*
Treatment Outcome
Tumor Necrosis Factor-alpha / metabolism

Substances

Biomarkers
Tumor Necrosis Factor-alpha

Grants and funding

R01 AI114587/AI/NIAID NIH HHS/United States