Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation
Year: 2023
Type: preprint
Study design: Observational Study
Abstract: 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.
Source: medRxiv
Authors: Jianing Fu, Thomas Hsiao, Elizabeth Waffarn, Wenzhao Meng, Katherine D. Long, Kristjana Frangaj, Rebecca Jones, Alaka Gorur, Areen Shtewe, Muyang Li, Constanza Bay Muntnich, Kortney Rogers, Wenyu Jiao, Monica Velasco, Rei Matsumoto, Masaru Kubota, Steven Wells, Nichole Danzl, Shilpa Ravella, Alina Iuga, Elena-Rodica Vasilescu, Adam Griesemer, Joshua Weiner, Donna L. Farber, Eline T. Luning Prak, Mercedes Martinez, Tomoaki Kato, Uri Hershberg, Megan Sykes
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1214792496, G1425971015, G210858417, G434337789, BD Biosciences Influx, ARCHITECTURE AND TOOLS FOR THE QUERY OF ANTIBODY AND T-CELL RECEPTOR SEQUENCING DATA REPOSITORIES FOR ENABLING IMPROVED PERSONALIZED MEDICINE AND IMMUNOTHERAPY, G674907753, Becton Dickinson LSR II Analytical Flow Cytometer, G9000000688, G9000127251, G9000138654, G9000175314, G9000176610, G9000266210
OpenAlex ID: W4388769381