Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization.
B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs.
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Chung
C
Park
Il-Young
IY
Hwang
Rajesh K
RK
Sinha
Olena
O
Kamenyeva
Michael D
MD
Davis
John H
JH
Kehrl
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003433:Crosses, Genetic; D015536:Down-Regulation; D006119:Groin; D007700:Kinetics; D008198:Lymph Nodes / Q000033:anatomy & histology / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008208:Lymphatic System / Q000033:anatomy & histology* / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D054400:Receptors, CCR7 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration
C515371:Ccr7 protein, mouse; D018925:Chemokines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D049349:Receptors, Lysosphingolipid