Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing.
Despite the established role for PI3Ks in cell migration, the PI3Ks involved in lymphocyte chemotaxis are poorly defined. In this study, we report that p110gamma-deficient T cells, but not B cells, show reduced chemotactic responses to the lymphoid chemokines, CCL19, CCL21, and CXCL12. As B cell and T cell chemotactic responses were both sensitive to the general PI3K inhibitors, wortmannin (WMN) and LY294002, we explored whether B cell responses were affected in mice lacking p110delta, a major PI3K isoform in lymphocytes. B cells deficient in p110delta showed diminished chemotactic responses, especially to CXCL13. Adoptive transfer experiments with WMN-treated wild-type B cells and with p110delta-deficient B cells revealed diminished homing to Peyer's patches and splenic white pulp cords. WMN selectively inhibited CXCR5-dependent B cell homing to Peyer's patches. These observations establish that p110gamma and p110delta function in lymphocyte chemotaxis, and show differential roles for PI3K family members in B and T cell migration.
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Karin
K
Reif
Klaus
K
Okkenhaug
Takehiko
T
Sasaki
Joseph M
JM
Penninger
Bart
B
Vanhaesebroeck
Jason G
JG
Cyster
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D018925:Chemokines / Q000276:immunology / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*
D018925:Chemokines; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases