Transitional and marginal zone B cells have a high proportion of unmasked CD22: implications for BCR signaling

CD22, a B cell‐specific member of the Siglec family, is an important inhibitor of B cell signaling. The first Ig‐like domain of CD22 specifically binds to α2,6‐linked sialic acids. Through these interactions CD22 can mediate adhesion to other cells in trans, but can also bind endogenous ligands on the B cell surface in cis. Cis binding of CD22 to sialylated ligands enhances the efficiency of inhibition and thereby reduces the BCR signaling strength. In this study we used a newly developed oligomeric streptavidin‐based sialylated probe as an artificial CD22 ligand. We found that CD22 is bound to ligands in cis on most B cells. However, there is a proportion of B cells with unbound (unmasked) CD22. The subpopulation with unmasked CD22 is 2‐fold increased in transitional and marginal zone B cells in the spleen and on B1 cells in the peritoneum, when compared to mature B cells. Also, B cells with unmasked CD22 have an activated phenotype. Unmasking of CD22 could be functionally involved in lowering the signaling threshold on developmental checkpoints such as transitional B cells and during B cell activation or could be a consequence of such activation processes.