Jason Cyster, PhD

Lymphocyte trafficking, Antibody Responses and Immune Regulation

Professor, Dept. of Microbiology and Immunology
Investigator, Howard Hughes Medical Institute
513 Parnassus Avenue, Room HSE 1001
San Francisco, CA 94143-0414

(415) 502-6427 tel
jason.cyster@ucsf.edu

Lab website

AA: Claire Chan, (415) 514-2943

Description of Research

As one of the most effective weapons in our anti-pathogen artillery, antibodies need to be made and released fast. The Cyster lab studies how lymphocytes are brought together to mount anti-pathogen antibody responses. This includes studies on chemokines and their receptors and the signals that regulate chemokine responses. Germinal centers are important sites for selection of high affinity B cells and by perturbing cell positioning in these microenvironments, the lab is characterizing the mechanism of affinity maturation. Lymphocytes need to exit lymphoid organs to reach sites of infection. The lab studies how the signaling lipid, sphingosine-1-phosphate (S1P), promotes cell exit from lymphoid tissues. In rare cases, antibody responses become uncontrolled, causing autoimmune diseases such as Lupus. In a further area of investigation, the lab studies the mechanisms responsible for regulating or deleting autoreactive B cells in peripheral lymphoid tissues. Genetic, RNAi, biochemical, expression array and cellular approaches are used to study these processes in mouse models and multiphoton microscopy is used to image cell-cell interactions in real-time.

Phan, T.G., Grigorova, I. , Okada, T. & Cyster, J.G . 2007. Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat. Immunol. doi: 10.1038/ni1494

Allen, C.D.C., Okada, T., Tang, H.L. and Cyster, J.G . 2007. Imaging of Germinal Center Selection Events During Affinity Maturation. Science 315, 528-31.

Pappu, R., Schwab, S.R., Cornelissen, I., Pereira, J.P., Regard, J.B., Xu, Y., Camerer, E., Zheng, Y-W., Huang, Y., Cyster, J.G . & Coughlin S.R. 2007. Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate. Science 316, 208-10.

Shiow, L.R., Rosen, D.B., Brdickova, N., Xu, Y., An, J., Lanier, L.L., and Cyster, J.G . and Matloubian, M. 2006. CD69 acts downstream of interferon-alpha/beta to inhibit S1P(1) and lymphocyte egress from lymphoid organs. Nature 440, 540-4.

Susan, S., Pereira , J.P., Matloubian, M., Xu, Y., Huang, Y. and Cyster, J.G . 2005. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309, 1735-1739.

Okada, T., Miller, M.J., Parker, I. , Krummel, M.F., Neighbors, M., Hartley, S.B., O'Garra, A., Cahalan, M.D. and Cyster, J.G . 2005. Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS Biology 3: e150.

Lesley, R., Xu, Y., Kalled, S.L., Hess, D.M., Schwab, S., Shu, H-B. and Cyster, J.G . 2004. Reduced competititveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity 4:441-453.