Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse

Complete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8—a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins—is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Galectin-8 triggers a faster recruitment and secretion of lysosomes toward the B cell-antigen contact site, resulting in efficient extraction of immobilized antigens through a proteolytic mechanism. Thus, extracellular cues can determine how B cells sense and extract tethered antigens and thereby tune B cell responses in vivo. Obino et al. report that Galectin-8 interacts with the BCR, promotes B cell arrest phases during surface-tethered antigen encounter, and facilitates synapse formation and lysosome secretion, which favors the proteolytic extraction of antigens. Consequently, Galectin-8 increases the capacity of B cells to present antigens to helper T cells in vivo.