Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development Journal Article
| Authors: | Bessler, M.; Rosti, V.; Peng, Y.; Cattoretti, G.; Notaro, R.; Ohsako, S.; Elkon, K. B.; Luzzatto, L. |
| Article Title: | Glycosylphosphatidylinositol-linked proteins are required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development |
| Abstract: | 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. |
| Keywords: | controlled study; somatic mutation; nonhuman; protein function; lymphocyte proliferation; t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; animal tissue; gene targeting; cell compartmentalization; apoptosis; cell maturation; membrane proteins; cell differentiation; homeodomain proteins; in vitro study; mice, inbred c57bl; b lymphocyte; cell lineage; chimera; immunoglobulin g; membrane protein; hematopoietic stem cells; stem cells; autoimmunity; blood cell; hematopoiesis; aging; antinuclear antibody; hematopoietic stem cell; mouse strain; mice, inbred cba; homeostasis; cell activation; lymphocytes; immunologic deficiency syndromes; lymphadenopathy; t lymphocyte activation; immunocompetence; knockout mouse; lymphocyte function; antibody titer; paroxysmal nocturnal hemoglobinuria; hemoglobinuria, paroxysmal; blastocyst; embryo transfer; embryo cell; lymphoproliferative disorders; delayed hypersensitivity; genetic complementation test; hypersensitivity, delayed; complementation; phosphatidylinositol; specific pathogen-free organisms; glycosylphosphatidylinositol; glycosylphosphatidylinositols; polyclonal activation; humans; female; priority journal; article; antibodies, antinuclear; pig-a- embryonic stem cell; rag-/- mouse; glypican; hypergammaglobulinemia |
| Journal Title: | European Journal of Immunology |
| Volume: | 32 |
| Issue: | 9 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2002-09-01 |
| Start Page: | 2607 |
| End Page: | 2616 |
| Language: | English |
| DOI: | 10.1002/1521-4141(200209)32:9<2607::aid-immu2607>3.0.co;2-h |
| PUBMED: | 12207345 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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