Deficient CCR7 signaling promotes T H 2 polarization and B‐cell activation in vivo

• Published in: European journal of immunology Vol. 42; no. 1; pp. 48 - 57
• Main Authors: Moschovakis, G. L., Bubke, Anja, Dittrich‐Breiholz, Oliver, Braun, Asolina, Prinz, Immo, Kremmer, Elisabeth, Förster, Reinhold
• Format: Journal Article
• Language: English
• Published: 01.01.2012
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141753

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.