Event Abstract

PI3K p110δ controls stromal cell distribution and is expressed in gp38+ stromal cells in secondary lymphoid organs

  • 1 Consejo Superior de Investigaciones Científicas, Spain
  • 2 Babraham Institute, United Kingdom
  • 3 Institute of Cancer (Queen Mary University of London), United Kingdom

Stromal cells create a network that physically supports lymphocyte displacement and anchorage of antigen-presenting cells and secrete chemokines involved in lymphocyte homing. Lack of PI3K p110δ subunit or catalytic activity in mice provokes structural anomalies in secondary lymphoid organs (SLO), which suggests a role for p110δ in their formation and maintenance. We tested whether lack of p110δ activity affects the immune response, not only through its role in lymphoid cells but also in stromal cells. We used p110δD910A/D910A mice, which express a catalytically inactive p110δ form, for bone marrow reconstitution assays. In lethally irradiated p110δWT/WT and p110δD910A/D910A mice reconstituted with total bone marrow from p110δWT/WT or p110δD910A/D910A donors, we studied total lymphoid cell number and the distribution of lymphoid cell subsets in homeostatic conditions and after antigen stimulation. We also analyzed the distribution and texture of SLO stromal cell populations in p110δWT/WT and p110δD910A/D910A mice and tested whether p110δ is expressed in those cells. Spleen structure in p110δWT/WT mice (organized) was similar to that of p110δWT/WT recipients reconstituted with p110δWT/WT or p110δD910A/D910A bone marrow, whereas that of p110δD910A/D910A mice (disorganized) was similar to that of p110δD910A/D910A mice reconstituted with p110δWT/WT or p110δD910A/D910A bone marrow. These findings suggest a role for p110δ in SLO stroma. p110δD910A/D910A SLO showed severe defects in T cell zone stromal cell distribution and impaired secretion of chemokines involved in T cell homing to SLO. Our data identify p110δ expression in gp38+ SLO stromal cell subsets and highlight the importance of these cells in immune response generation.

Keywords: lymphoid stroma, PI3K p110δ, secondary lymphoid organs, reconstitution, gp38+ cells

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Innate immunity

Citation: Zotes TM, Pérez-Yagüe S, Spada R, Sorzano CO, Okkenhaug K, Vanhaesebroeck B, Carrera AC and Barber DF (2013). PI3K p110δ controls stromal cell distribution and is expressed in gp38+ stromal cells in secondary lymphoid organs
. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00427

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Received: 04 Apr 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Domingo F Barber, Consejo Superior de Investigaciones Científicas, Madrid, Spain, dfbarber@cnb.csic.es