Journal
HUMAN IMMUNOLOGY
Volume 79, Issue 5, Pages 380-387Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2018.02.007
Keywords
Transplantation; Kidney; Tolerance; Biomarkers; B cells
Categories
Funding
- National Institute of Allergy and Infectious Disease [N01 AI15416, UM1 AI-109565]
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Studies of kidney transplant recipients who have developed spontaneous and sustained tolerance have revealed an association with B cells. Unexpectedly tolerant individuals are characterized by increased numbers and frequencies of B cells in the blood and increased expression of genes associated with B cells in the blood and urine. Comparisons of the B cell repertoires of tolerant individuals and those receiving immunosuppression reveal that not only are the B cells more numerous but developmental differences result in a repertoire comprised of more naive and transitional B cells in the tolerant cohort. B cells isolated from tolerant individuals also display functional differences compared to those from individuals receiving immunosuppression. Many of these differences may serve to suppress alloimmunity. Lastly a significant number of transplant recipients receiving standard immunosuppression display B cell-biased patterns of gene expression predictive of tolerance or a protolerogenic state. Interestingly, this pattern is associated with improved renal allograft function. While recent studies have raised the concern that immunosuppressive drugs heavily influence B cell-based signatures of tolerance, a substantial body of work suggests that differences in B cells may be a useful tool for identifying tolerant kidney transplant recipients or guiding their immunosuppressive management.
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