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Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo

✍ Scribed by G. L. Moschovakis; Anja Bubke; Oliver Dittrich-Breiholz; Asolina Braun; Immo Prinz; Elisabeth Kremmer; Reinhold Förster


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
376 KB
Volume
42
Category
Article
ISSN
0014-2980

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✦ Synopsis


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 naı ¨ve CD4 1 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 1 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.