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

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.