Journal article
Phenotypic and Clonal Analysis of Recipient B cells and Plasma Cells Entering Graft Mucosa Reveals an Association with Rejection and Evolution towards a Resident Memory Phenotype after Human Intestinal Transplantation
Transplantation, v 102 Suppl 7S-1(Supplement 7), pp S15-S16
Jul 2018
Abstract
Alloantibodies produced by recipient B cells and plasma cells pose a significant risk for rejection after solid organ transplantation, including intestinal transplantation (ITx). Dynamic turnover of recipient B cells and plasma cells in intestinal allografts and their roles in mediating rejection have not been investigated.We analyzed the chimerism, phenotype and clonotypes of B cells and plasma cells in the allograft and peripheral blood of ITx recipients using multicolor flow cytometry and high-throughput BCR sequencing.Serial analyses of ileal biopsies demonstrated eventual replacement of lamina propria donor B cells by the recipient, over periods of >1 year in some patients (Fig.1). Recipient B cell replacement rates were often faster than those of T cells. In patients with donor T cell macrochimerism (>4%) in blood, replacement of donor cells by recipient cells tended to occur slowly, over a period of several months. In contrast, in patients without T cell macrochimerism and with early rejection, recipient B cells and T cells rapidly replaced those of the donor in the graft. High levels (>10%) of donor B cell chimerism in blood were only observed in multivisceral transplant (MVTx) recipients and peak donor B cell blood chimerism was generally higher than that of donor T cells within the same patient.Phenotypic analyses of lamina propria B cells on sequential biopsies of a 2-year-old recipient of an allograft from a 6-month-old donor revealed the early presence of naïve donor and recipient B cells in the graft that over time were largely replaced by both class-switched and non-switched memory B cells of donor and recipient origin. Recipient-derived surface IgG and IgA B cells appeared in the long-term graft of a patient who had had DSA but not in a DSA patient. Even when recipient B cells had almost fully replaced donor-derived B cells, donor-derived plasma cells (CD138CD38) persisted long-term (POD>900), demonstrating the existence of long-lived plasma cells in human intestine. The presence of recipient plasma cells in the graft may correlate with rejection, as they were only detected during rejection episodes. (Fig.2).IgH V region sequencing on sorted recipient B cells from ileal specimens of a MVTx patient on Days 29, 32, 43, 57, 78, 105 and 141 post-Tx revealed clonal overlap, especially at later time points. The fraction of recipient B cells co-expressing CD45RB and CD69 in the ileal biopsies increased with time in 3 out of 3 patients. (Fig.3) CD45RBCD69 B cells may belong to a resident memory pool that contributes to tissue-based immunity (Weisel et al, in preparation).In summary, the appearance of recipient plasma cells and IgG/IgA B cells in the graft correlates with rejection and DSA development, respectively. We hypothesize that graft-repopulating recipient B cell clones may expand and acquire a B resident memory phenotype, promoting organ-specific alloimmunity.
(Figure is included in full-text article.)(Figure is included in full-text article.)(Figure is included in full-text article.)
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- Title
- Phenotypic and Clonal Analysis of Recipient B cells and Plasma Cells Entering Graft Mucosa Reveals an Association with Rejection and Evolution towards a Resident Memory Phenotype after Human Intestinal Transplantation
- Creators
- Jianing Fu - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesElizabeth Waffarn - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesBrittany Shonts - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesWenzhao Meng - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDora Chen - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesSuxiao Yang - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesSiu-hong Ho - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesJulien Zuber - Columbia Center for Translational Immunology, Columbia University, New York, NY, United StatesNadine Weisel - Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United StatesMark Shlomchik - Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United StatesUri Hershberg - Drexel UniversityEline Prak - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesMercedes Martinez - Department of Pediatrics, Columbia University, New York, NY, United StatesTomoaki Kato - Department of Surgery, Columbia University, New York, NY, United StatesMegan Sykes - Columbia Center for Translational Immunology, Columbia University, New York, NY, United States
- Publication Details
- Transplantation, v 102 Suppl 7S-1(Supplement 7), pp S15-S16
- Publisher
- Copyright Wolters Kluwer Health, Inc. All rights reserved
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000444541200024
- Other Identifier
- 991019167330004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Surgery
- Transplantation