Document Detail


Development of systemic lupus erythematosus in NZM 2328 mice in the absence of any single BAFF receptor.
MedLine Citation:
PMID:  23334904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the necessity for any individual BAFF receptor in the development of systemic lupus erythematosus (SLE).
METHODS: Bcma-, Taci-, and Br3-null mutations were introgressed into NZM 2328 mice. NZM.Bcma-/-, NZM.Taci-/-, and NZM.Br3-/- mice were evaluated for lymphocyte phenotype and BAFF receptor expression by flow cytometry; for B cell responsiveness to BAFF by in vitro culture; for serum levels of BAFF and total IgG and IgG anti-double-stranded DNA (anti-dsDNA) by enzyme-linked immunosorbent assay; for renal immunopathology by immunofluorescence and histopathology; and for clinical disease.
RESULTS: BCMA, TACI, and B lymphocyte stimulator receptor 3 (BR3) were not surface-expressed in NZM.Bcma-/-, NZM.Taci-/-, and NZM.Br3-/- mice, respectively. Transitional and follicular B cells from NZM.Br3-/- mice were much less responsive to BAFF than were the corresponding cells from wild-type, NZM.Bcma-/-, or NZM.Taci-/- mice. In comparison with wild-type mice, NZM.Bcma-/- and NZM.Taci-/- mice harbored an increased number of spleen B cells, T cells, and plasma cells, whereas serum levels of total IgG and IgG anti-dsDNA were similar to those in wild-type mice. Despite their paucity of B cells, NZM.Br3-/- mice had an increased number of T cells, and the numbers of plasma cells and levels of IgG anti-dsDNA were similar to those in wild-type mice. Serum levels of BAFF were increased in NZM.Taci-/- and NZM.Br3-/- mice but were decreased in NZM.Bcma-/- mice. Despite their phenotypic differences, NZM.Bcma-/-, NZM.Taci-/-, and NZM.Br3-/- mice had renal immunopathology and clinical disease that were at least as severe as that in wild-type mice.
CONCLUSION: Any single BAFF receptor, including BR3, is dispensable for the development of SLE in NZM mice. Development of disease in NZM.Br3-/- mice demonstrates that BAFF-BCMA and/or BAFF-TACI interactions contribute to SLE, and that a profound, life-long reduction in the numbers of B cells does not guarantee protection against SLE.
Authors:
Chaim O Jacob; Ning Yu; Shunhua Guo; Noam Jacob; William J Quinn; Vishal Sindhava; Michael P Cancro; Beatrice Goilav; Chaim Putterman; Thi-Sau Migone; William Stohl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-22     Revised Date:  2014-07-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1043-54     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Antinuclear
B-Cell Activating Factor / pharmacology
B-Cell Activation Factor Receptor / genetics,  metabolism
B-Cell Maturation Antigen / genetics,  metabolism*
B-Lymphocyte Subsets* / cytology,  drug effects,  metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Immunoglobulin G / immunology,  metabolism
Immunoglobulin M / immunology,  metabolism
Kidney / immunology,  metabolism,  pathology
Lupus Erythematosus, Systemic / etiology,  immunology,  metabolism*
Mice
Mice, Congenic
Transmembrane Activator and CAML Interactor Protein / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
P30 CA016520/CA/NCI NIH HHS; R01 AR048692/AR/NIAMS NIH HHS; R01 AR050193/AR/NIAMS NIH HHS; R01 DK090319/DK/NIDDK NIH HHS; R01-AI-057473/AI/NIAID NIH HHS; R01-AI-073939/AI/NIAID NIH HHS; R01-AR-048692/AR/NIAMS NIH HHS; R01-AR-050193/AR/NIAMS NIH HHS; R01-DK-090319/DK/NIDDK NIH HHS; T32-AI-055428/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/B-Cell Activating Factor; 0/B-Cell Activation Factor Receptor; 0/B-Cell Maturation Antigen; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Tnfrsf13b protein, mouse; 0/Tnfrsf13c protein, mouse; 0/Tnfrsf17 protein, mouse; 0/Tnfsf13b protein, mouse; 0/Transmembrane Activator and CAML Interactor Protein
Comments/Corrections

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