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

Abstract

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.