| Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice. | |
| | |
MedLine Citation:
|
PMID: 20181885 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1-25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1-25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology. |
| | |
Authors:
|
St?phanie Lacotte; H?l?ne Dumortier; Marion D?cossas; Jean-Paul Briand; Sylviane Muller |
Related Documents
:
|
1090665 - Effect of cortisone on the disappearance kinetics and tissue localization of soluble im... 9138445 - Induction of experimental antiphospholipid antibody syndrome in pl/j mice following imm... 161855 - Therapeutic effect of beta-[1-phenyl-5-bis(beta-chloroethyl)-amino-benzimidazolyl-(2)-d... 14512165 - Increased icam-1 and vcam-1 expression in the brains of autoimmune mice. 3939485 - Progestin regulation of progesterone biosynthetic enzymes in cultured rat granulosa cells. 3374085 - Inapparent streptococcus pneumoniae type 35 infections in commercial rats and mice. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-24 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-03-22 Completed Date: 2010-04-27 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 3937-45 Citation Subset: AIM; IM |
Affiliation:
|
Centre National de la Recherche Scientifique, Institut de Biologie Mol?culaire et Cellulaire, Immunologie et Chimie Th?rapeutiques, Strasbourg, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Autoantibodies / blood, immunology* Autoantigens / immunology B-Lymphocytes / immunology* Enzyme-Linked Immunosorbent Assay Female Histones / immunology* Immunoblotting Immunohistochemistry Lupus Nephritis / blood, immunology* Mice Mice, Inbred BALB C Mice, Inbred NZB |
| Chemical | |
Reg. No./Substance:
|
0/Autoantibodies; 0/Autoantigens; 0/Histones |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: CpG-B oligodeoxynucleotides inhibit TLR-dependent and -independent induction of type I IFN in dendri...
Next Document: Clcn5 Knockout Mice Exhibit Novel Immunomodulatory Effects and Are More Susceptible to Dextran Sulfa...