B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis.
Sphingosine-1-phosphate (S1P) helps mediate lymphocyte egress from lymph nodes, yet many mechanistic questions remain. Here, we show the presence of B lymphocyte egress sites located in the lymph node cortex close to lymph node follicles. B cells exited lymph nodes by squeezing through apparent portals in the lymphatic endothelium of these sinusoids. Treatment with the S1P receptor agonist FTY720 emptied the cortical sinusoids of lymphocytes, blocked lymphatic endothelial penetration, and displaced B lymphocytes into the T cell zone. S1pr3(-/-) B cells, which lack chemoattractant responses to S1P, transited lymph nodes normally, whereas Gnai2(-/-) B cells, which have impaired responses to chemokines and S1P, transited more rapidly than did wild-type cells. This study identifies a major site of B lymphocyte lymph node egress, shows that FTY720 treatment blocks passage through the cortical lymphatic endothelium, and argues against a functional role for S1P chemotaxis in B lymphocyte egress.
Sinha
Rajesh K
RK
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892-1876, USA.
Park
Chung
C
Hwang
Il-Young
IY
Davis
Michael D
MD
Kehrl
John H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement; D002633:Chemotaxis; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine