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

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Humoral immunity depends on naive B cell recruitment to lymph nodes (LN) and differentiation into antibody-producing cells.
• The factors coordinating B cell adhesion, activation, and differentiation within LNs are not fully understood.
• Galectin-9 (Gal-9) has been implicated as a negative regulator of B cell receptor (BCR) signaling.

Purpose of the Study:

• To investigate the role of Galectin-9 (Gal-9) in naive B cell trafficking and activation within human lymph nodes.
• To elucidate the mechanisms by which Gal-9 influences B cell interactions with endothelial cells (EC).

Main Methods:

• Immunohistochemical analysis of Gal-9 expression in human tonsils and LNs.
• In vitro adhesion assays to assess B cell binding to ECs in the presence of Gal-9.
• Analysis of gene transcription and signaling pathways in B cells upon Gal-9 interaction.

Main Results:

• High expression of Gal-9 was observed on high endothelial venules and post-capillary venules in human LNs.
• Gal-9 mediated the adhesion of naive B cells to vascular ECs and reduced their transendothelial migration.
• Gal-9 binding induced global gene transcription related to cell signaling and cytoskeletal dynamics.
• Gal-9 upregulated Signaling lymphocytic activation molecule F7 (SLAMF7) but decreased its adapter EAT-2, while activating ERK phosphorylation.

Conclusions:

• Galectin-9 promotes B cell adhesion to endothelial cells within lymph nodes.
• Gal-9 delivers signals that attenuate B cell reactivity, potentially inducing anergy.
• These findings reveal a novel role for Gal-9 in regulating B cell homing and immune responses.