# Analysis of vascular Galectin-9 as an immunomodulator of B-cell activity > **NIH NIH R21** · FLORIDA INTERNATIONAL UNIVERSITY · 2020 · $204,670 ## Abstract PROJECT ABSTRACT Development of effective antibody (Ab) responses is critically dependent on the recruitment of naïve B cells into secondary lymphoid organs and, upon antigen activation, their coordinated differentiation into germinal center (GC) B cells to memory B cells and Ab-producing plasma cells. Knowing which mechanistic factors control B cell subset transition with the therapeutic goal of Ab-boosting or -attenuating activity, however, is still poorly understood. Exciting new published data from our laboratory highlight striking differences in the glycomic signatures of human naïve, GC and memory B cell subsets featured by either i-linear or I-branched poly-N-acetyllactosamines (poly-LacNAcs). Whereas GC B cells express mainly I-branched poly-LacNAcs, naïve/memory B cells display principally i-linear poly-LacNAcs, which enable robust binding to immuno- modulator, galectin (Gal)-9. Gal-9-binding causes downstream inhibition of cell proliferation, activation and signaling related to BCR-engagement while, interestingly, evoking a pro-survival activity. Given the selective Gal-9-binding to naive/memory B cells, we speculate that Gal-9 serves as a physiologic “tuner” of peripheral B cell activation and B cell reactivity. Other key data on the distribution of Gal-9 in “reactive” lymph node (LN)- like tonsil tissue reveal that, while naïve B cells express endogenous Gal-9, Gal-9 expression is strongest on high endothelial venules (HEV). Since HEVs initiate adhesive contact with circulating naïve/memory B cells and are densely packed in the cortex adjacent to B cell follicles, HEVs are strategically poised to elicit Gal-9- dependent adhesion/regulation. The spatial, cellular and functional control of Gal-9 on B cells in lymphoid organs is still unknown and a major gap in the field of galectin immunology. Our guiding hypothesis is that Gal- 9 on HEV can bind circulating naïve/memory B cells and help recruit them into LNs as well as transmit regulatory signals as B cells traverse the endothelium and enter B cell follicles. In this exploratory proposal, we will examine the function of human endothelial cell (EC)-derived Gal-9 on human naïve B cell adhesion and immunoregulation and will assay for B cell homing to peripheral LNs in the presence/absence of Gal-9. The Specific Aims are: 1.) To study Gal-9-dependent vascular EC – B cell adhesive interactions and 2.) To analyze immunoregulatory effects of Gal-9 expressed by cytokine-activated human ECs on human naïve B cells. We will employ our unique experience and innovative primary human cell models, adhesion assays, mutant mice, gene editing methods to study whether Gal-9 on ECs supports naïve B cell adhesion, LN-homing as well as trigger immunoregulatory activity. These exploratory studies directly challenge current dogma that galectins largely function as immunoregulators, offering an alternative role for Gal-9 in facilitating B cell-EC adhesion, LN-homing and in situ peripheral control of B cell act... ## Key facts - **NIH application ID:** 9981626 - **Project number:** 5R21AI146368-02 - **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY - **Principal Investigator:** CHARLES J DIMITROFF - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $204,670 - **Award type:** 5 - **Project period:** 2019-08-15 → 2021-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9981626 ## Citation > US National Institutes of Health, RePORTER application 9981626, Analysis of vascular Galectin-9 as an immunomodulator of B-cell activity (5R21AI146368-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981626. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*