A Dual Role for Src Homology 2 Domain–Containing Inositol-5-Phosphatase (Ship) in Immunity

• DOI: 10.1084/jem.191.5.781
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Cheryl D. Helgason; Christian P. Kalb...; Jacqueline E. Damen; Suzanne M. Chappel; Nicolas Pineault; Gerald Krystal; R. Keith Humphries
• Keywords: B-Lymphocytes; Immunity, Cellular; Myeloproliferative Disorders; Cell Cycle; Apoptosis; Bone Marrow Cells; Mice, SCID; Flow Cytometry; Mice, Mutant Strains; Phosphoric Monoester Hydrolases; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Immunoglobulin M; Mice, Inbred NOD; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Animals; Ficoll; Lymph Nodes; Mitogen-Activated Protein Kinases; Phosphorylation; Bone Marrow Transplantation

In this report, we demonstrate that the Src homology 2 domain–containing inositol-5-phosphatase (SHIP) plays a critical role in regulating both B cell development and responsiveness to antigen stimulation. SHIP−/− mice exhibit transplantable alteration lymphoid results reduced numbers of precursor (fraction C) immature cells bone marrow. vitro, purified enhanced proliferation response receptor stimulation presence absence Fcγ IIB coligation. This enhancement is associated with increased phosphorylation mitogen-activated protein kinase Akt, as well survival cycling. manifest elevated serum immunoglobulin (Ig) levels an exaggerated IgG T cell–independent type trinitrophenyl Ficoll. However, only altered was apparent upon transplantation into nonobese diabetic–severe combined immunodeficient (NOD/SCID) mice. The vitro hyperresponsiveness, together vivo findings, suggests SHIP regulates by intrinsic extrinsic mechanisms.