| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610; North Florida South George Veterans Health System, Gainesville, FL 32608; and Center for Immunology, Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75235
Lupus pathogenesis in the NZM2410 mouse model results from the expression of multiple interacting susceptibility loci. Sle2 on chromosome 4 was significantly linked to glomerulonephritis in a linkage analysis of a NZM2410 x B6 cross. Yet, Sle2 expression alone on a C57BL/6 background did not result in any clinical manifestation, but in an abnormal B cell development, including the accumulation of B-1a cells in the peritoneal cavity and spleen. Analysis of B6.Sle2 congenic recombinants showed that at least three independent loci, New Zealand White-derived Sle2a and Sle2b, and New Zealand Black-derived Sle2c, contribute to an elevated number of B-1a cells, with Sle2c contribution being the strongest of the three. To determine the contribution of these three Sle2 loci to lupus pathogenesis, we used a mapping by genetic interaction strategy, in which we bred them to B6.Sle1.Sle3 mice. We then compared the phenotypes of these triple congenic mice with that of previously characterized B6.Sle1.Sle2.Sle3, which express the entire Sle2 interval in combination with Sle1 and Sle3. Sle2a and Sle2b, but not Sle2c, contributed significantly to lupus pathogenesis in terms of survival rate, lymphocytic expansion, and kidney pathology. These results show that the Sle2 locus contains several loci affecting B cell development, with only the two NZW-derived loci having the least effect of B-1a cell accumulation significantly contributing to lupus pathogenesis.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  V. Parravicini, A.-C. Field, P. D. Tomlinson, M. Albert Basson, and R. Zamoyska Itch-/-{alpha}{beta} and {gamma}{delta} T cells independently contribute to autoimmunity in Itchy mice Blood, April 15, 2008; 111(8): 4273 - 7282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.R.N. e Brito, B.H.P. De Lorenzo, P. Xander, L.C. Godoy, J.D. Lopes, N.P. da Silva, S.C. Sampaio, and M. Mariano Role of distinct immune components in the radiation-induced abrogation of systemic lupus erythematosus development in mice Lupus, December 1, 2007; 16(12): 947 - 954. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Miwa, M. A. Maldonado, L. Zhou, K. Yamada, G. S. Gilkeson, R. A. Eisenberg, and W.-C. Song Decay-Accelerating Factor Ameliorates Systemic Autoimmune Disease in MRL/lpr Mice via Both Complement-Dependent and -Independent Mechanisms Am. J. Pathol., April 1, 2007; 170(4): 1258 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Loh, Y.-C. Cai, G. Bonventi, G. Lajoie, R. MacLeod, and J. E. Wither Dissociation of the Genetic Loci Leading to B1a and NKT Cell Expansions from Autoantibody Production and Renal Disease in B6 Mice with an Introgressed New Zealand Black Chromosome 4 Interval J. Immunol., February 1, 2007; 178(3): 1608 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wan, C. Xia, and L. Morel IL-6 Produced by Dendritic Cells from Lupus-Prone Mice Inhibits CD4+CD25+ T Cell Regulatory Functions J. Immunol., January 1, 2007; 178(1): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shen, C. Zhang, T. Wang, S. Brooks, R. J. Ford, Y. C. Lin-Lee, A. Kasianowicz, V. Kumar, L. Martin, P. Liang, et al. Development of Autoimmunity in IL-14{alpha}-Transgenic Mice J. Immunol., October 15, 2006; 177(8): 5676 - 5686. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
