Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B cells

CD22 is a B cell-specific transmembrane protein known to function as a nega tive regulator of B cell signaling. It has also been implicated in cell adh esion through recognition of alpha 2,6-linked sialic acids on glycans of ta rget cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow desp ite normal B cell development. Using a soluble recombinant form of the rece ptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are ex pressed on sinusoidal endothelial cells of murine bone marrow but not on en dothelial cells in other tissues examined. Injection of CD22-Fc revealed th at the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibo dy led to an similar to 50% reduction in mature recirculating B cells in th e bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobuli n M-secreting plasma cells in the bone marrow.