dc.contributor.author | Merino, R | |
dc.contributor.author | Iwamoto, M | |
dc.contributor.author | Fossati, L | |
dc.contributor.author | Muniesa, P | |
dc.contributor.author | Araki, K | |
dc.contributor.author | Takahashi, S | |
dc.contributor.author | Huarte, J | |
dc.contributor.author | Yamamura, K | |
dc.contributor.author | Vassalli, JD | |
dc.contributor.author | Izui, S | |
dc.date.accessioned | 2021-05-13T15:01:23Z | |
dc.date.available | 2021-05-13T15:01:23Z | |
dc.date.issued | 1993-10-01 | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/71801 | |
dc.description.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. | en_US |
dc.format.extent | 1189 - 1197 | |
dc.language | eng | |
dc.relation.ispartof | J Exp Med | |
dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
dc.subject | Animals | en_US |
dc.subject | Autoimmunity | en_US |
dc.subject | Cells, Cultured | en_US |
dc.subject | Female | en_US |
dc.subject | Histocompatibility Antigens Class II | en_US |
dc.subject | Lupus Erythematosus, Systemic | en_US |
dc.subject | Male | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Inbred Strains | en_US |
dc.subject | Mice, Transgenic | en_US |
dc.title | Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain. | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1084/jem.178.4.1189 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/8376928 | en_US |
pubs.issue | 4 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 178 | en_US |