PMID- 28422925
DCOM- 20171106
LR  - 20180216
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 101
IP  - 11
DP  - 2017 Nov
TI  - Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients.
PG  - 2722-2730
LID - 10.1097/TP.0000000000001789 [doi]
AB  - 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.
FAU - Gao, Baoshan
AU  - Gao B
AD  - 1 Transplant Center, Massachusetts General Hospital, Harvard Medical School,
      Boston, MA. 2 Transplant Center, The First Hospital of Jilin University,
      Changchun, China. 3 Columbia Center for Translational Immunology, Department of
      Medicine, Columbia University Medical Center, New York, NY. 4 The Affiliated
      Hospital to Changchun University of Chinese Medicine, Changchun, China. 5
      Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA.
FAU - Gu, Yiming
AU  - Gu Y
FAU - Rong, Chunshu
AU  - Rong C
FAU - Moore, Carolina
AU  - Moore C
FAU - Porcheray, Fabrice
AU  - Porcheray F
FAU - Wong, Waichi
AU  - Wong W
FAU - Preffer, Frederic
AU  - Preffer F
FAU - Saidman, Susan L
AU  - Saidman SL
FAU - Fu, Yaowen
AU  - Fu Y
FAU - Cosimi, Benedict
AU  - Cosimi B
FAU - Sachs, David H
AU  - Sachs DH
FAU - Kawai, Tatsuo
AU  - Kawai T
FAU - Sykes, Megan
AU  - Sykes M
FAU - Zorn, Emmanuel
AU  - Zorn E
LA  - eng
GR  - R01 DK083352/DK/NIDDK NIH HHS/United States
GR  - UM1 AI109565/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Biomarkers)
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - B-Lymphocytes/*immunology/metabolism
MH  - Biomarkers/blood
MH  - *Bone Marrow Transplantation
MH  - Boston
MH  - *Cell Proliferation
MH  - Female
MH  - Genes, Immunoglobulin Heavy Chain
MH  - Graft Survival
MH  - HLA Antigens/immunology
MH  - Hospitals, General
MH  - Humans
MH  - Immunologic Memory
MH  - Isoantibodies/blood
MH  - *Kidney Transplantation
MH  - Lymphocyte Count
MH  - Male
MH  - Mutation
MH  - Phenotype
MH  - Recovery of Function
MH  - Time Factors
MH  - Transplantation Tolerance
MH  - Treatment Outcome
PMC - PMC5648631
MID - NIHMS867541
EDAT- 2017/04/20 06:00
MHDA- 2017/11/07 06:00
CRDT- 2017/04/20 06:00
PMCR- 2018/11/01 00:00
PHST- 2018/11/01 00:00 [pmc-release]
PHST- 2017/04/20 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2017/04/20 06:00 [entrez]
AID - 10.1097/TP.0000000000001789 [doi]
PST - ppublish
SO  - Transplantation. 2017 Nov;101(11):2722-2730. doi: 10.1097/TP.0000000000001789.