Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing

César Nombela-Arrieta, Rosa Ana Lacalle, María C. Montoya, Yuya Kunisaki, Diego Megías, Miriam Marqués, Ana C. Carrera, Santos Mañes, Yoshinori Fukui, Carlos Martínez-A, Jens V. Stein

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188 Citations (Scopus)

Abstract

Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kγ, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2-/- B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kγ thus play distinct roles during T and B cell integrin activation and migration.

Original languageEnglish
Pages (from-to)429-441
Number of pages13
JournalImmunity
Volume21
Issue number3
DOIs
Publication statusPublished - Sep 1 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Nombela-Arrieta, C., Lacalle, R. A., Montoya, M. C., Kunisaki, Y., Megías, D., Marqués, M., Carrera, A. C., Mañes, S., Fukui, Y., Martínez-A, C., & Stein, J. V. (2004). Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing. Immunity, 21(3), 429-441. https://doi.org/10.1016/j.immuni.2004.07.012