title: Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma.
abstract: The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Changxi
authors.initials: C
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiaojing
authors.identifier: 0000-0001-8564-3539
authors.initials: X
authors.lastname: Zeng
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Du
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Lin
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Fu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, 5110 Oberndorf, Austria.
authors.forename: Ursula Huber
authors.identifier: 0000-0003-4674-6230
authors.initials: UH
authors.lastname: Schoenauer
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, 5110 Oberndorf, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlmayr
authors.affiliation: American Medical Global Exchange, Sydney, New South Wales 2145, Australia; and.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
authors.affiliation: First Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
authors.affiliation: Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, 5110 Oberndorf, Austria; liuxiao@genomics.cn C.Datz@kh-oberndorf.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; liuxiao@genomics.cn C.Datz@kh-oberndorf.at.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
mesh_terms: D000236:Adenoma / Q000276:immunology* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000502:physiology*; D001706:Biopsy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D019295:Computational Biology; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell