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

J Autoimmun. 2021 Feb;117:102575. doi: 10.1016/j.jaut.2020.102575. Epub 2020 Dec 4.

Abstract

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.

Keywords: B cell tolerance; Cell adhesion; Galectins; Humoral immunity; Immunoregulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Biomarkers
  • Cell Adhesion
  • Cell Communication / immunology
  • Cell Differentiation / immunology
  • Cell Movement
  • Endothelium, Vascular / metabolism*
  • Galectins / metabolism*
  • Humans
  • Immunohistochemistry
  • Immunomodulation*
  • Immunophenotyping
  • Lymphocyte Activation
  • Protein Transport
  • Signal Transduction*

Substances

  • Biomarkers
  • Galectins
  • LGALS9 protein, human