The Sweetness of migration:

Abstract

Galectin-9 helps govern human B cell adhesion to and migration through human vascular endothelium

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 Lee Seng Lau1, Asmi Chakraborty1, Caleb Staudinger1, Sandra L. King2, Frances Clemente Erickson1, Angela Bernasconi1, Francis W. Luscinskas3, Chad Perlyn4, Charles J. Dimitroff1

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1Department of Translational Medicine, Translational Glycobiology Institute at FIU, Florida International University, Miami, FL; 2Department of Dermatology, Brigham and Women’s Hospital, Boston, MA 02115; 3Department of Pathology, Vascular Research Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; 4Nicholas Children’s Hospital Ambulatory Surgery Center and Department of Surgery, Division of Plastic Surgery, Herbert Wertheim College of Medicine Florida International University, Miami, FL

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Humoral immunity is driven by the coordinated differentiation of naïve B cells into antibody-secreting plasma cells. For naive B cells to access peripheral lymph node (LN) and reside awaiting activation by pathogenic antigen, there is a requirement for circulating naïve B cells to adhere and be retained in LNs. Though lymphocyte (L)-selectin is the LN-homing receptor for all lymphocytes, the role of L-selectin in B cell homing to peripheral LN is less clear. Prior data from our laboratory indicate that circulating naïve B cells express an abundance of i-linear glycans that avidly bind galectin (Gal)-9 and that Gal-9 is expressed at a high level in peripheral LNs. We hypothesize that Gal-9 may play a role in circulating B cell homing to peripheral LNs. In this study, we analyzed human circulating B cells for their expression of homing molecules, L-selectin and endothelial (E)-selectin-binding glycans, sLeX/A, and found that L-selectin was expressed at low level and sLeX/A antigens were absent. We investigated the ability of Gal-9 to mediate adhesion between human naïve B cells and human vascular endothelial cells. We observed Gal-9-dependent adhesion of B cells to HUVEC that was inhibited in absence of Gal-9 or presence of competitive inhibitor lactose. These data illustrate Gal-9’s role in circulating B cell homing to peripheral LN and/or in retention of naïve B cells in LNs. Our studies implicate Gal-9 in the adhesion of human B cells to vascular endothelium and provide a putative mechanism for Gal-9 controlling the efficiency of humoral immune responses.