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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4129-4133.
Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-06-2075.
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Submitted June 2, 2004
Accepted August 6, 2004
FTY720 Suppresses Humoral Immunity by Inhibiting Germinal Center Reaction
Shuhua Han, Xuejun Zhang, Gangdou Wang, Hui Guan, Gabriela Garcia, Ping Li, Lili Feng, and Biao Zheng*
Department of Immunology, Baylor College of Medicine, Houston, TX, USA
Department of Medicine, Baylor College of Medicine, Houston, TX, USA
* Corresponding author; email: bzheng{at}bcm.tmc.edu.
FTY720 is a novel immunosuppressant that is highly effective in inhibiting rejection of allografts and autoimmunity in various animal models. It has been shown that the sphingosine 1-phosphate (S1P) receptors are the direct molecular targets of FTY720. However, the mechanisms responsible for inhibiting specific immune responses by FTY720 are not well resolved. In particular, there is no available information on whether or how this compound affects humoral immunity. We have investigated the effect of FTY720 treatment on B cell response during the immune response to a well-defined T-dependent antigen. Our data demonstrated that germinal center reaction was significantly reduced in peripheral lymphoid tissues of mice treated with FTY720. In addition, FTY720 treatment inhibited the production of high-affinity, class-switched antibodies, but not low affinity, IgM antibody production. Consistently, FTY720 did not have a significant effect on antibody response to a T-independent antigen. Our results may have important implications in application of FTY 720 in immune regulation.
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