TY - JOUR
T1 - A novel proangiogenic B cell subset is increased in cancer and chronic inflammation
AU - van de Veen, Willem
AU - Globinska, Anna
AU - Jansen, Kirstin
AU - Straumann, Alex
AU - Kubo, Terufumi
AU - Verschoor, Daniëlle
AU - Wirz, Oliver F
AU - Castro-Giner, Francesc
AU - Tan, Ge
AU - Rückert, Beate
AU - Ochsner, Urs
AU - Herrmann, Marietta
AU - Stanić, Barbara
AU - van Splunter, Marloes
AU - Huntjens, Daan
AU - Wallimann, Alexandra
AU - Fonseca Guevara, Rodney J
AU - Spits, Hergen
AU - Ignatova, Desislava
AU - Chang, Yun-Tsan
AU - Fassnacht, Christina
AU - Guenova, Emmanuella
AU - Flatz, Lukas
AU - Akdis, Cezmi A
AU - Akdis, Mübeccel
N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2020/5
Y1 - 2020/5
N2 - B cells contribute to immune responses through the production of immunoglobulins, antigen presentation, and cytokine production. Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell clones to identify an IgG4+ B cell subset with a unique function. These B cells are characterized by simultaneous expression of proangiogenic cytokines including VEGF, CYR61, ADM, FGF2, PDGFA, and MDK. Consequently, supernatants from these clones efficiently promote endothelial cell tube formation. We identified CD49b and CD73 as surface markers identifying proangiogenic B cells. Circulating CD49b+CD73+ B cells showed significantly increased frequency in patients with melanoma and eosinophilic esophagitis (EoE), two diseases associated with angiogenesis. In addition, tissue-infiltrating IgG4+CD49b+CD73+ B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.
AB - B cells contribute to immune responses through the production of immunoglobulins, antigen presentation, and cytokine production. Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell clones to identify an IgG4+ B cell subset with a unique function. These B cells are characterized by simultaneous expression of proangiogenic cytokines including VEGF, CYR61, ADM, FGF2, PDGFA, and MDK. Consequently, supernatants from these clones efficiently promote endothelial cell tube formation. We identified CD49b and CD73 as surface markers identifying proangiogenic B cells. Circulating CD49b+CD73+ B cells showed significantly increased frequency in patients with melanoma and eosinophilic esophagitis (EoE), two diseases associated with angiogenesis. In addition, tissue-infiltrating IgG4+CD49b+CD73+ B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.
KW - B-Lymphocyte Subsets/metabolism
KW - Cytokines/metabolism
KW - Eosinophilic Esophagitis
KW - Humans
KW - Immunoglobulin G
KW - Inflammation
KW - Integrin alpha2
KW - Melanoma/genetics
UR - https://www.scopus.com/pages/publications/85084785792
U2 - 10.1126/sciadv.aaz3559
DO - 10.1126/sciadv.aaz3559
M3 - Article
C2 - 32426497
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 20
M1 - eaaz3559
ER -
SDG 3 Good Health and Well-being