| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,¶
* Arthritis Centre of Excellence, Toronto Western Research Institute, Toronto, Ontario, Canada;
Department of Immunology and
Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada;
Department of Medicine, University Health Network, Toronto, Ontario, Canada; and
¶ Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
Polyclonal B cell activation is a prominent feature of the lupus-prone New Zealand Black (NZB) mouse strain. We have previously demonstrated linkage between a region on NZB chromosome 13 and increased costimulatory molecule expression on B cells. In this study we have produced C57BL/6 congenic mice with an introgressed homozygous NZB interval extending from 
24 to 73 cM on chromosome 13 (denoted B6.NZBc13). We show that B6.NZBc13 female mice not only have enhanced B cell activation but also share many other B cell phenotypic characteristics with NZB mice, including expansion of marginal zone and CD5+ B cell populations, increased numbers of IgM ELISPOTs, and increased serum levels of total IgM and IgM autoantibodies. In addition these mice have increased T cell activation, increased numbers of germinal centers, mild glomerulonephritis, and produce high-titer IgM and IgG anti-chromatin Abs. Male B6.NZBc13 mice have a less pronounced cellular phenotype, lacking expansion of the marginal zone B cell population and IgG anti-chromatin Ab production, indicating the presence of gender dimorphism for this locus. Thus, we have identified a genetic locus that recapitulates with fidelity the B cell phenotypic abnormalities in NZB mice, and we demonstrate that this locus is sufficient to induce an autoimmune phenotype. The data provide further support to the contention that immune abnormalities leading to altered B cell activation and selection contribute to the development of autoimmunity in NZB mice.
This article has been cited by other articles:
|
|
 |
|
  Y. Moriyama, C. Sekine, A. Koyanagi, N. Koyama, H. Ogata, S. Chiba, S. Hirose, K. Okumura, and H. Yagita Delta-like 1 is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice Int. Immunol., April 1, 2008; (2008) dxn034v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Raveche, E. Salerno, B. J. Scaglione, V. Manohar, F. Abbasi, Y.-C. Lin, T. Fredrickson, P. Landgraf, S. Ramachandra, K. Huppi, et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice Blood, June 15, 2007; 109(12): 5079 - 5086. [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]
|
|
|
|
|
|
C. O. Jacob, L. Pricop, C. Putterman, M. N. Koss, Y. Liu, M. Kollaros, S. A. Bixler, C. M. Ambrose, M. L. Scott, and W. Stohl Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF J. Immunol., August 15, 2006; 177(4): 2671 - 2680. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
