AI Article Synopsis
- Previous studies indicated that specific B cell signatures might play a role in achieving operational tolerance after kidney transplants, suggesting their importance in tolerance maintenance.
- The research involved analyzing B cell recovery in four patients, focusing on their B cell subsets, heavy chain repertoire, and serum reactivity to HLA using advanced techniques like flow cytometry and next-generation sequencing.
- Results showed that while B cell counts generally recovered a year post-transplant, one individual's delayed reconstitution led to complications; however, memory B cells were prominent early after transplantation, indicating a potential link to developing tolerance, prompting further investigation into these cells' functions.
Article Abstract
Background: Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance after kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation.
Methods: Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next-generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex.
Results: B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated immunoglobulin heavy chain variable sequences and transient serum reactivity to HLA.
Conclusions: Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648631 | PMC |
| http://dx.doi.org/10.1097/TP.0000000000001789 | DOI Listing |
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