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

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 differe...

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Veröffentlicht in:Journal of autoimmunity 2021-02, Vol.117, p.102575-102575, Article 102575
Hauptverfasser: Chakraborty, Asmi, Staudinger, Caleb, King, Sandra L., Erickson, Frances Clemente, Lau, Lee Seng, Bernasconi, Angela, Luscinskas, Francis W., Perlyn, Chad, Dimitroff, Charles J.
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Sprache:eng
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Zusammenfassung: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. •Human naïve B cells use galectin-9 to bind vascular endothelium and restrict TEM.•Galectin-9-binding triggers global immunoregulatory pathways in human naïve B cells.•Galectin-9-binding globally restricts cellular dynamics pathways in human naïve B cells.•Galectin-9-binding promotes human naïve B cell survival.•Galectin-9-binding engages a SLAMF7-inhibitory pathway in human naïve B cells.
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2020.102575