Expression of α4β7 and E‐selectin ligand by circulating memory B cells: implications for targeted trafficking to mucosal and systemic sites

We have examined the expression of homing receptors on circulating memory B cells subsets. Blood IgD + (naive) B cells homogeneously express a high level of intestinal homing receptor, α4β7, but IgD − (putative memory) B cells comprise distinct α4β7 + and α4β7 − subsets. Naive and α4β7 + memory B cells but not α4β7 − cells bind MAdCAM‐1, suggesting that α4β7 expression may predict B cell intestinal homing. In contrast, α4β7 + and α4β7 − B cells bind well to VCAM‐1, possibly allowing recruitment of both subsets to extra‐intestinal sites, including those tissues of the “common mucosal immune system” characterized by vascular VCAM‐1 expression. sIgA + B cells, which are associated with mucosal immunity in the gut and elsewhere, are heterogeneous in homing receptor expression—with discrete subsets expressing α4β7, L‐selectin, and cutaneous lymphocyte antigen (CLA). sIgA + CLA + B cells are enriched by binding to E‐selectin, suggesting that CLA may participate in B cell homing to nonintestinal mucosal tissues characterized by vascular E‐selectin expression, such as chronically inflamed bronchial or oral mucosal. We conclude that circulating human peripheral blood memory B cells, like T cells, consist of discrete homing receptor‐defined subsets. This diversity in homing phenotypes is apparent even among sIgA (presumptive mucosal) memory B cells, implying heterogeneity in trafficking mechanisms to different target mucosal surfaces.