International Immunology, Vol. 16, No. 3, pp. 517-524,
March 2004
© 2004 Japanese Society for Immunology
Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human peripheral blood mononuclear cells
1 INSERM Unité 430 and Université Pierre et Marie Curie, Institut des Cordeliers, 75006 Paris, France 2 Institute of Cell Biology, National Research Council, Campus ‘A. Buzzati-Traverso’, 00016 Monterotondo Scalo (Rome), Italy 3 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Correspondence to: S. V. Kaveri; E-mail: srini.kaveri{at}u430.bhdc.jussieu.fr
Transmitting editor: I. Pecht
Natural polyreactive IgM autoantibodies, encoded by unmutated germline Ig V genes, represent a major fraction of the normal circulating IgM repertoire. We have previously shown that therapeutic preparation of pooled IgM exerts immunomodulatory effects as assessed by in vitro and in vivo studies. Here, we show that the IgM preparation induces cell death in lymphoblastoid cell lines and in human peripheral blood mononuclear cells. The IgM-induced cell death involved classical features of apoptosis such as nuclear fragmentation and activation of caspases. Treatment of leukemic cells with IgM resulted in the cleavage of poly-(A)DP ribose polymerase, a substrate of caspase, and in a reduction in mitochondrial transmembrane potential during the early period of apoptosis induction. Natural IgM-induced apoptosis was inhibited by soluble Fas molecules and affinity-purified Fas antibodies from pooled IgM preparation induced apoptosis in lymphoblastoid cells, suggesting the involvement of the Fas receptor. Our results suggest a role for normal IgM in controlling cell death and proliferation, and imply a possible therapeutic role for IgM in autoimmune and lymphoproliferative disorders.
Keywords: caspase, Fas, immunomodulation, IVIgM