CD72 down-modulates BCR-induced signal transduction and diminishes survival in primary mature B lymphocytes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Daniel H LiJ R Parnes

Abstract

CD72, a 45-kDa type II transmembrane glycoprotein carrying an ITIM motif, is believed to be an inhibitory coreceptor of the BCR. Mature B cells lacking CD72 show enhanced Ca(2+) mobilization and are hyperproliferative in response to BCR ligation. However, the signal transduction pathways downstream of BCR signaling that transmit the inhibitory effect of CD72 in mature B cells remain unknown. To address this question, we used hen egg lysozyme-specific BCR transgenic mice to elucidate the differential cell signaling between wild-type and CD72-deficient B cells in response to hen egg lysozyme Ag stimulation. Our results demonstrate that CD72 predominantly down-regulates the major signal transduction pathways downstream of the BCR, including NF-AT, NF-kappaB, ERK, JNK, p38-MAPK, and PI3K/Akt in mature B cells. CD72 ligation with anti-CD72 Ab (K10.6), which mimics the binding of CD100 (a natural ligand for CD72) to release the inhibitory function of CD72, augments cell proliferation, Ca(2+) flux, IkappaBalpha activation, and ERK MAPK activity upon Ag stimulation in wild-type B cells. In addition, we show direct evidence that CD72 promotes cell cycle arrest and apoptosis after Ag stimulation in mature B cells. Taken together, our fin...Continue Reading

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Citations

Jul 27, 2007·Hematology·Dino VeneriRiccardo Ortolani
Jan 27, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatsuki R KataokaAlasdair M Gilfillan
Apr 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miduo XuTakeshi Tsubata
Apr 5, 2017·Leukemia & Lymphoma·Rosa BoschCarol Moreno
May 1, 2017·Clinical Reviews in Allergy & Immunology·Taher E TaherRizgar A Mageed
Dec 11, 2008·Journal of Clinical Immunology·Hsin-Jung Wu, Subbarao Bondada
Jan 1, 2013·Scientific Reports·Tatsuki R KataokaHironori Haga
Sep 30, 2008·Arthritis and Rheumatism·Daniel Hsieh-Hsin LiJane R Parnes
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Dan SuJeremy A Daniel
May 12, 2018·Molecular Cancer Therapeutics·Michela BardiniGianni Cazzaniga

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