Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation.

Autor:	Fu J; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Hsiao T; Department of Human Biology, University of Haifa, Haifa, Israel., Waffarn E; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Meng W; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA., Long KD; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Frangaj K; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Jones R; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Gorur A; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Shtewe A; Department of Human Biology, University of Haifa, Haifa, Israel., Li M; Department of Pathology, Columbia University, New York, NY, USA., Muntnich CB; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Rogers K; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Jiao W; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Velasco M; Department of Pediatrics, Columbia University, New York, NY, USA., Matsumoto R; Department of Microbiology and Immunology, Columbia University, New York, NY, USA., Kubota M; Department of Microbiology and Immunology, Columbia University, New York, NY, USA., Wells S; Department of Microbiology and Immunology, Columbia University, New York, NY, USA., Danzl N; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA., Ravella S; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA., Iuga A; Department of Pathology, Columbia University, New York, NY, USA., Vasilescu ER; Department of Pathology, Columbia University, New York, NY, USA., Griesemer A; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA.; Department of Surgery, Columbia University, New York, NY, USA., Weiner J; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA.; Department of Surgery, Columbia University, New York, NY, USA., Farber DL; Department of Microbiology and Immunology, Columbia University, New York, NY, USA.; Department of Surgery, Columbia University, New York, NY, USA., Luning Prak ET; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA., Martinez M; Department of Pediatrics, Columbia University, New York, NY, USA., Kato T; Department of Surgery, Columbia University, New York, NY, USA., Hershberg U; Department of Human Biology, University of Haifa, Haifa, Israel., Sykes M; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA.; Department of Microbiology and Immunology, Columbia University, New York, NY, USA.; Department of Surgery, Columbia University, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Nov 16. Date of Electronic Publication: 2023 Nov 16.
DOI:	10.1101/2023.11.15.23298517
Abstrakt:	It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of gut lymphocyte populations. Using polychromatic flow cytometry that includes HLA allele group-specific mAbs distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. We confirm the early presence of naïve donor B cells in the circulation and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa. Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in healthy control adults. Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of establishment of a stable mucosal B cell repertoire. Competing Interests: Declaration of interests The authors declare no competing interests.
Databáze:	MEDLINE
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