Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways. Issue 117 (February 2021)

• Record Type: Journal Article
• Authors: Chakraborty, Asmi; Staudinger, Caleb; King, Sandra L.; Erickson, Frances Clemente; Lau, Lee Seng; Bernasconi, Angela; Luscinskas, Francis W.; Perlyn, Chad; Dimitroff, Charles J.
• Is Part Of: Journal of autoimmunity. Issue 117(2021)
• Publication Date: 2021-02
• Subjects: B cell tolerance -- Humoral immunity -- Galectins -- Cell adhesion -- Immunoregulation; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2020.102575
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: 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.