Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development

Monica Bessler, Vittorio Rosti, Yufeng Peng, Giorgio Cattoretti, Rosario Notaro, Satomi Ohsako, Keith B. Elkon, Lucio Luzzatto

Research output: Contribution to journalArticlepeer-review


Surface proteins tethered to the membrane through a glycosylphosphatidylinositol (GPI) anchor are deficient in the blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) as result of a somatic mutation, in a hematopoietic stem cell, of the X-linked phosphatidylinositolglycan complementation group A (PIG-A) gene. In PNH patients, compared to the large numbers of GPI-deficient myeloid cells, the proportion of GPI-deficient lymphocytes tends to be low, and therefore the impact of GPI deficiency on immune function has been unclear. We have obtained complementation by Pig-a- embryonic stem (ES) cells of Rag-/- blastocysts, and we show that Pig-a- ES cells are able to reconstitute the T cell and B cell compartments of Rag-/- mice. Although these mice were immunologically competent, by comparison with appropriate controls we detected several abnormalities: (1) increased levels of IgG; (2) high frequency/titers of anti-nuclear antibodies; (3) markedly reduced delayed hypersensitivity; and (4) impaired activation-induced lymphocyte death in vitro. In some cases, aging Pig-a-/Rag-/- chimeric mice developed lymphadenopathy and polyclonal T cell and B cell expansion. Thus, GPI-linked proteins are not required for lymphocyte development but they are required for normal lymphocyte function and for maintaining normal peripheral lymphoid homeostasis.

Original languageEnglish
Pages (from-to)2607-2616
Number of pages10
JournalEuropean Journal of Immunology
Issue number9
Publication statusPublished - Sep 2002


  • Complementation
  • Knockout mouse
  • Paroxysmal nocturnal hemoglobinuria
  • Pig-a embryonic stem cell
  • Rag mouse

ASJC Scopus subject areas

  • Immunology


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