The Journal of Immunology CD22 Is a Recycling Receptor That Can Shuttle Cargo between the Cell Surface and Endosomal Compartments of

CD22 is a member of the sialic acid-binding Ig-like lectin (Siglec) family that is known to be a regulator of B cell signaling. Its B cell-specific expression makes it an attractive target for immunotoxin-mediated B cell depletion therapy for the treatment of B cell lymphomas and autoimmune diseases. Although CD22 is well documented to be an endocytic receptor, it is believed that after internalization, it is targeted for degradation. We show in this study that CD22 is instead constitutively recycled to the cell surface. We also find that glycan ligand-based cargo is released fromCD22 and accumulates intracellularly as CD22 recycles between the cell surface and endosomal compartments. In contrast, Abs to CD22 do not accumulate but remain bound to CD22 and recycle to the cell surface. The results have implications for development of agents that target CD22 as an endocytic receptor for delivery of cytotoxic cargo to B cells. The Journal of Immunology, 2011, 186: 1554–1563. C D22 is a member of a family of sialic acid-binding, Ig-like lectins (Siglecs) that are involved in regulation of cellular activation receptors and cell–cell adhesion (1, 2). The primary function of CD22 is to regulate the BCR through re-cruitment of the phosphatase Shp1 upon Ag stimulation (3–6). Contributing to this function in ways that are not completely un