ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1745

Amelioration of Experimental Autoimmune Arthritis by Adoptive Transfer of Foxp3-Expressing Regulatory B Cells Is Associated with the Regulatory T Cell/T helper 17 cell Balance

Young Ok Jung1, Yu Jung Heo2, Mi Kyung Park3, Mi-La Cho4, Seung Ki Kwok5, Ji Hyeon Ju2, Kyung Su PARK2, Sung Hwan PARK2, Ho Youn Kim2 and Jun-Ki Min6, 1Internal Medicine Hallym University Kangnam Sacred Heart Hospital, Seoul, South Korea, 2Catholic University, Seoul, South Korea, 3Rheumatism Research Center (RhRC), The Catholic University of Korea, Seoul, South Korea, 4Rheumatism Research Center, Catholic Research Institute of Medical Science, Catholic University of Korea, Seoul, South Korea, 5The Catholic University, Seoul, South Korea, 6Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: B-cell Biology and Targets in Autoimmune Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Foxp3 is a key regulator of the development and function of regulatory T cells (Tregs), and its expression is thought to be T cell-restricted. We hypothesized that B cells can express Foxp3 and B cells expressing Foxp3 may play a role in preventing the development of collagen-induced arthritis (CIA).

Methods: Protein and mRNA expression of Foxp3 in CD19+ B cells from mice was determined by flow cytometry, western blotting, and RT-PCR. Confocal microscopy was used to visualize the location and expression of Foxp3 in B and T cells. Foxp3 expression was modulated in CD19+ B cells by transfection with shRNA or using an over-expression construct. In vitro suppressive activity of Foxp3-expressing B cells on T cell proliferation was assessed by a 3H-thymidine incorporation assay. In addition, Foxp3-transfected B cells were adoptively transferred to CIA mice. Therapeutic effects were evaluated by clinical symptoms and joint histopathology.

Results: We found that lipopolysaccharide (LPS) or anti-IgM stimulation induced Foxp3 expression in B cells. Foxp3-expressing B cells were found in the spleens of mice. To generate Foxp3-expressing B cells in vitro, we transfected CD19+ B cells with a Foxp3 over-expression construct. Over-expression of Foxp3 conferred a contact-dependent suppressive ability on proliferation of responder T cells. Down-regulation of Foxp3 by shRNA caused a profound reduction in proliferation of responder T cells. Adoptive transfer of Foxp3+CD19+ B cells attenuated the clinical symptoms of CIA significantly with concomitant suppression of IL-17 production and enhancement of Foxp3 expression in CD4+ T cells from splenocytes.

Conclusion: Our data indicate that Foxp3 expression is not restricted to T cells. The expression of Foxp3 in B cells is critical for the immunoregu­lation of T cells and limits autoimmunity in a mouse model.

Disclosure:

Y. O. Jung,
None;

Y. J. Heo,
None;

M. K. Park,
None;

M. L. Cho,
None;

S. K. Kwok,
None;

J. H. Ju,
None;

K. S. PARK,
None;

S. H. PARK,
None;

H. Y. Kim,
None;

J. K. Min,
None.

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