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Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain

Merino, R.
Iwamoto, M.
Fossati-Jimack, Liliane
Muniesa, P.
Araki, K.
Takahashi, S.
Yamamura, K.
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Published in The Journal of experimental medicine. 1993, vol. 178, no. 4, p. 1189-1197
Abstract Males from the BXSB murine strain (H-2b) spontaneously develop an autoimmune syndrome with features of systemic lupus erythematosus (SLE), which results in part from the action of a mutant gene (Yaa) located on the Y chromosome. Like other H-2b mice, the BXSB strain does not express the class II major histocompatibility complex antigen, I-E. Here we report that the expression of I-E (E alpha dE beta b) in BXSB males bearing an E alpha d transgene prevents hypergammaglobulinemia, autoantibody production, and subsequent autoimmune glomerulonephritis. These transgenic mice bear on the majority of their B cells not only I-E molecules, but also an I-E alpha chain-derived peptide presented by a higher number of I-Ab molecules, as recognized by the Y-Ae monoclonal antibody. The I-E+ B cells appear less activated in vivo than the I-E- B cells, a minor population. This limited activation of the I-E+ B cells does not reflect a functional deficiency of this cell population, since it can be stimulated to IgM production in vitro by lipopolysaccharides at an even higher level than the I-E- B cell population. The development of the autoimmune syndrome in the transgenic and nontransgenic bone marrow chimeric mice argues against the possibility that the induction of regulatory T cells or clonal deletion of potential autoreactive T cells as a result of I-E expression is a mechanism of the protection conferred by the E alpha d transgene. We propose a novel mechanism by which the E alpha d transgene protects BXSB mice against SLE: overexpression of I-E alpha chains results in the generation of excessive amounts of a peptide displaying a high affinity to the I-Ab molecule, thereby competing with pathogenic autoantigen-derived peptides for presentation by B lymphocytes and preventing their excessive stimulation.
Keywords AnimalsAutoimmunityCells, CulturedFemaleHistocompatibility Antigens Class II/genetics/ physiologyLupus Erythematosus, Systemic/genetics/immunology/ prevention & controlMaleMiceMice, Inbred StrainsMice, Transgenic
PMID: 8376928
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MERINO, R. et al. Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain. In: The Journal of experimental medicine, 1993, vol. 178, n° 4, p. 1189-1197. doi: 10.1084/jem.178.4.1189 https://archive-ouverte.unige.ch/unige:8895

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Deposited on : 2010-07-12

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