4ß7 and E-selectin ligand by circulating memory B cells: implications for targeted trafficking to mucosal and systemic sites
* Laboratory of Immunology and Vascular Biology, Department of Pathology and the Digestive Disease Center, Stanford University, Stanford, California;
Center for Molecular Biology and Medicine, Veterans Administration Medical Center, Palo Alto, California
LeukoSite, Inc., Cambridge, Massachusetts
Correspondence: Lusijah S. Rott, Veterans Administration Medical Center, 3801 Miranda Ave., 154B, Palo Alto, CA 94304. E-mail: lrott{at}cmgm.stanford.edu
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,
4ß7, but IgD- (putative memory) B cells comprise
distinct 4ß7+ and 4ß7- subsets.
Naive and 4ß7+ memory B cells but not
4ß7- cells bind MAdCAM-1, suggesting that 4ß7
expression may predict B cell intestinal homing. In contrast,
4ß7+ and 4ß7- 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 4ß7, 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.
Key Words: mucosal immunity • cutaneous lymphocyte antigen (CLA) • MAdCAM-1 addressin • IgA • homing • trafficking
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