CD22 is a B-cell-restricted transmembrane protein, which acts as a negative regulator of B-cell signalling. CD22 also has lectin-like adhesive properties. When expressed on transfected fibroblasts, it is capable of mediating adhesion to other cells via recognition of cell-surface glycoconjugates terminating in alpha2,6-linked sialic acids. In previous studies in the mouse, CD22 was implicated as a bone marrow homing receptor for recirculating immunoglobulin D+ (IgD(+)) B cells through recognition of sialylated ligands on marrow sinusoidal endothelium. As the adhesive function of CD22 can be masked when alpha2,6-linked sialic acids are co-expressed at the cell surface, the aim of the present study was to investigate whether recirculating B cells have unmasked forms of CD22 that could be involved in bone marrow homing. Using alpha2,6-sialyllactose coupled to biotinylated polyacrylamide as a probe for detection of unmasked CD22, we showed that approximate to 2-5% of IgD(+) murine B cells in the spleen and mesenteric lymph nodes were able to bind this synthetic ligand. In the bone marrow, however, the fraction of IgD(+) B cells with unmasked CD22 was increased by two- to fivefold. B cells from CD22-deficient mice were not stained with the polyacrylamide probe, confirming that staining of B cells in wild-type mice was caused by CD22 and not by other potential sialic acid-binding lectins. In conclusion, we have identified a new subset of mature B cells in the mouse with unmasked CD22. This subset of recirculating B cells may bind to CD22 ligands on bone marrow sinusoidal endothelium, leading to their selective homing and subsequent enrichment in this tissue.