| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Research Service, Harry S. Truman Memorial Veteran’s Affairs Hospital, Columbia, MO 65201;
Department of Internal Medicine and
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212; and
Biogen Idec, San Diego, CA 92122
B cells are important for the development of most autoimmune diseases. B cell depletion immunotherapy has emerged as an effective treatment for several human autoimmune diseases, although it is unclear whether B cells are necessary for disease induction, autoantibody production, or disease progression. To address the role of B cells in a murine model of spontaneous autoimmune thyroiditis (SAT), B cells were depleted from adult NOD.H-2h4 mice using anti-mouse CD20 mAb. Anti-CD20 depleted most B cells in peripheral blood and cervical lymph nodes and 50–80% of splenic B cells. Flow cytometry analysis showed that marginal zone B cells in the spleen were relatively resistant to depletion by anti-CD20, whereas most follicular and transitional (T2) B cells were depleted after anti-CD20 treatment. When anti-CD20 was administered before development of SAT, development of SAT and anti-mouse thyroglobulin autoantibody responses were reduced. Anti-CD20 also reduced SAT severity and inhibited further increases in anti-mouse thyroglobulin autoantibodies when administered to mice that already had autoantibodies and thyroid inflammation. The results suggest that B cells are necessary for initiation as well as progression or maintenance of SAT in NOD.H-2h4 mice.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Merit Review Grant from the Department of Veterans Affairs, the Arthritis National Research Foundation, Children’s Miracle Network, and the Lottie Caroline Hardy Trust.
2 Address correspondence and reprint requests to Dr. Helen Braley-Mullen, Department of Internal Medicine, Division of Immunology and Rheumatology, University of Missouri, M307 Health Science Center, One Hospital Drive, Columbia, MO 65212. E-mail address: mullenh{at}health.missouri.edu
3 Abbreviations used in this paper: SAT, spontaneous autoimmune thyroiditis; MTg, mouse thyroglobulin; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; MZ, marginal zone; FO, follicular; CLN, cervical lymph node; hCD20, human CD20.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
