Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.

Autor: Chakraborty A; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., Staudinger C; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., King SL; Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA., Erickson FC; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., Lau LS; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., Bernasconi A; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., Luscinskas FW; Department of Pathology, Vascular Research Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Perlyn C; Department of Surgery, Nicholas Children's Hospital, Division of Plastic Surgery, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA., Dimitroff CJ; Department of Translational Medicine, Translational Glycobiology Institute at FIU, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA. Electronic address: cdimitroff@fiu.edu.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2021 Feb; Vol. 117, pp. 102575. Date of Electronic Publication: 2020 Dec 04.
DOI: 10.1016/j.jaut.2020.102575
Abstrakt: Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7's cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell - EC interactions while delivering anergic signals to control B cell reactivity.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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