title: Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo.
abstract: The chemokine receptor CCR7 has a central role in regulating homing and positioning of T cells and DCs to lymph nodes (LNs) and participates in T-cell development and activation. In this study, we addressed the role of CCR7 signaling in T(H) 2 polarization and B-cell activation. We provide evidence that the lack of CCR7 drives the capacity of naïve CD4(+)  T cells to polarize toward T(H) 2 cells. This propensity contributes to a lymph node environment in CCR7-deficent mice characterized by increased expression of IL-4 and increased frequency of T(H) 2 cells. We show that elevated IL-4 levels lead to B-cell activation characterized by up-regulated expression of MHC class II, CD23 and CD86. Activated B cells are in turn highly efficient in presenting antigen to CD4(+)  T cells and thus potentially contribute to the T(H) 2 microenvironment. Taken together, our results support the idea of a CCR7-dependent patterning of T(H) 2 responses, with absent CCR7 signaling favoring T(H) 2 polarization, dislocation of T helper cells into the B-cell follicles and, as a consequence, B-cell activation.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: G L
authors.initials: GL
authors.lastname: Moschovakis
authors.forename: Anja
authors.initials: A
authors.lastname: Bubke
authors.forename: Oliver
authors.initials: O
authors.lastname: Dittrich-Breiholz
authors.forename: Asolina
authors.initials: A
authors.lastname: Braun
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051940:B7-2 Antigen / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D005260:Female; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D054400:Receptors, CCR7; D017455:Receptors, IgE; D015847:Interleukin-4; D012313:RNA