title: Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.
abstract: It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not α4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Coelho
authors.forename: Daniela
authors.initials: D
authors.lastname: Natale
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Soriano
authors.forename: Miroslav
authors.initials: M
authors.lastname: Hons
authors.forename: Jim
authors.initials: J
authors.lastname: Swoger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mayer
authors.forename: Renzo
authors.initials: R
authors.lastname: Danuser
authors.forename: Elke
authors.initials: E
authors.lastname: Scandella
authors.forename: Markus
authors.initials: M
authors.lastname: Pieczyk
authors.forename: Hans-Günter
authors.initials: HG
authors.lastname: Zerwes
authors.forename: Tobias
authors.initials: T
authors.lastname: Junt
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sailer
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: James
authors.initials: J
authors.lastname: Sharpe
authors.forename: Marc Thilo
authors.initials: MT
authors.lastname: Figge
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism* / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: C514936:CXCR4 protein, mouse; C513179:CXCR5 protein, mouse; C515371:Ccr7 protein, mouse; D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5