Expression of alpha4beta7 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, alpha4beta7, but IgD- (putative memory) B cells comprise distinct alpha4beta7+ and alpha4beta7- subsets. Naive and alpha4beta7+ memory B cells but not alpha4beta7- cells bind MAdCAM-1, suggesting that alpha4beta7 expression may predict B cell intestinal homing. In contrast, alpha4beta7+ and alpha4beta7- 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 alpha4beta7, 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.
Rott
L S
LS
Department of Pathology and the Digestive Disease Center, Stanford University, California, USA. lrott@cmgm.stanford.edu
Briskin
M J
MJ
Butcher
E C
EC
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D004064:Digestive System / Q000276:immunology; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007072:Immunoglobulin D / Q000032:analysis; D007136:Immunoglobulins / Q000378:metabolism; D007156:Immunologic Memory; D016023:Integrins / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009061:Mouth Mucosa / Q000276:immunology; D009088:Mucoproteins / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology; D009928:Organ Specificity; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D012137:Respiratory System / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015415:Biomarkers; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007071:Immunoglobulin A, Secretory; D007072:Immunoglobulin D; D007136:Immunoglobulins; D016023:Integrins; C504265:MADCAM1 protein, human; D008562:Membrane Glycoproteins; D009088:Mucoproteins; D011947:Receptors, Antigen, B-Cell; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; D019041:L-Selectin