CXCL13 is an arrest chemokine for B cells in high endothelial venules.
Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13-/- mice and that B-cell adhesion is substantially restored in CXCL13-/- HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating alpha4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine (C8), 2-2, Yamada-oka, Suita, 565-0871, Japan.
Naotoshi
N
Kanemitsu
Yukihiko
Y
Ebisuno
Toshiyuki
T
Tanaka
Kazuhiro
K
Otani
Haruko
H
Hayasaka
Tsuneyasu
T
Kaisho
Shizuo
S
Akira
Koko
K
Katagiri
Tatsuo
T
Kinashi
Naoya
N
Fujita
Takashi
T
Tsuruo
Masayuki
M
Miyasaka
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D014699:Venules / Q000166:cytology / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D015815:Cell Adhesion Molecules; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D007136:Immunoglobulins; D016023:Integrins; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D018799:Intercellular Adhesion Molecule-1; D020827:rap1 GTP-Binding Proteins