Professor Ji-Yang Wang
Lymphocyte Differentiation Research Group
Department of Immunology
School of Basic Medical Sciences Fudan University
Mailbox 226, 138 Yi Xue Yuan Road
Shanghai 200032, China
Tel: (+86) 21-5423-7957 (direct)
(+86) 21-5423-7432 (administrative staff)
Email: wang@fudan.edu.cn
Lab Staff and Students
Associate professor
Weijuan Zhang
Assistant professor
Qing Lu
Postdoctoral fellow
Yingqian Li
Graduate students
Jun Liu Qin Lin Rongjian Hong Yang Zhou
Undergraduate student Trainees
Zhe Wang Xiaoyan Tang Dandan Liu Yue Li Xiaoyao Fan
Ming Lei Qing Min Jingwen Wu Xi Wu
Administrative staff
Lumin Zhang
Research Interests
Antibodies are crucial effectors for host defense mediated by neutralization and opsonization of pathogens and by activation of the complement system. Antibodies are also important regulators of immune responses, acting through binding to the Fc receptors expressed by various immune cells. Insufficient or excess production of antibodies can lead to immunodeficiencies or autoimmune diseases, respectively. The goal of our current research is to understand how B cell activation and differentiation are positively and negatively regulated to achieve effective humoral immunity and to prevent autoimmune diseases.
Research projects
1)Uncover new pathways that regulate B cell activation and differentiation through analysis of mice with inactivating mutations in B cell-specific genes
We have identified several uncharacterized genes that are exclusively expressed in B cells, including the germinal center (GC) subset of B cells and other subsets and established knockout mice for these genes. Through analysis of these mutant mice, we hope to uncover new pathways that regulate B cell development, survival, activation, and differentiation. We will also explore the role of these genes in immunological diseases.
2)Elucidate the function of the IgM Fc receptor in the humoral immune response
One of the B cell-specific genes turned out to be the receptor for IgM (FcμR). In collaboration with the Laboratory for Epithelial Immunobiology of RIKEN and the University of Alabama at Birmingham, we have shown that FcμR positively regulates B cell survival, activation and GC formation, and is required for efficient humoral immune responses. Intriguingly, FcμR-/- mice produce autoantibodies as they age. Studies are in progress to clarify the molecular mechanism by which FcμR promotes immunity against foreign antigens and tolerance to self-antigens.
3)Explore the mechanism of Ig gene somatic hypermutation
High-affinity antibodies are central to humoral immunity. Somatic hypermutation (SHM) of Ig genes in GC B cells is an essential process for generating high-affinity B cells. SHM is initiated by the activation-induced cytidine deaminase (AID), which is thought to convert cytosine (C) to uracil (U) and generate U:G lesions on DNA. We have identified a putative form of AID that appears to inhibit the hypermutating activity of AID. We aim to elucidate the nature of this unique form to further understand the mechanism of Ig gene hypermutation.
Selected publications
1. Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T. and Wang, J.-Y. LAPTM5 promotes lysosomal degradation of intracellular but not the cell surface CD3ζ. Immunol. Cell Biol., in press (2014).
2. Ouchida, R., Mori, H., Ohno, H. and Wang, J.-Y. FcμR (Toso/Faim3) is not an inhibitor of Fas-mediated cell death in mouse T and B cells. Blood 121: 2368-2370 (2013).
3. Ouchida, R., Mori, H., Hase, K., Takatsu, H., Kurosaki, T., Tokuhisa, T., Ohno, H. and Wang, J.-Y. Critical role of the IgM Fc receptor in IgM homeostasis, B cell survival and humoral immune responses. Proc. Natl. Acad. Sci. USA 109: E2699-2706 (2012). (Faculty of 1000)
4. Ouchida, R., Mori, H., Hase, K., Takatsu, H., Kurosaki, T., Tokuhisa, T., Ohno, H. and Wang, J.-Y. Critical role of the IgM Fc receptor in IgM homeostasis, B cell survival and humoral immune responses. Proc. Natl. Acad. Sci. USA 109: 15989-15990. (Author Summary) (2012).
5. Imai, T., Kato, Y., Kajiwara, C., Mizukami, S., Ishige, I., Ichiyanagi, T., Hikida, M., Wang, J.-Y. and Udono, H. Hsp90 contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. Proc. Natl. Acad. Sci. USA 108: 16363-16368 (2011).
6. Ouchida, R., Kurosaki, T. and Wang, J.-Y. A role for lysosomal-associated protein transmembrane 5 in the negative regulation of surface BCR levels and B cell activation. J. Immunol. 185: 294-301 (2010).
7. Kubagawa, H., Oka, S., Kubagawa, Y., Torii, I., Takayama, E., Kang, D.W., Gartland, G.L., Bertoli, L.F., Mori, H., Takatsu, H., Kitamura, T., Ohno, H. and Wang, J.-Y. Identity of the elusive IgM Fc receptor (FcµR) in humans. J. Exp. Med. 206: 2779-2793 (2009).
8. Masuda, K., Ouchida, R., Li, Y., Gao, X., Mori, H. and Wang, J.-Y. A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during immunoglobulin gene hypermutation. J. Immunol. 183: 1846-1850 (2009).
9. Ukai, A., Ishimaru, K., Ouchida, R., Mori, H., Kano, C., Moritan, T. and Wang, J.-Y. Induction of A:T mutations is dependent on cellular environment but independent of mutation frequency and target gene location. J. Immunol. 181: 7835-7842 (2008).
10. Masuda, K., Ouchida, R., Yokoi, M., Hanaoka, F., Azuma, T. and Wang, J.-Y. DNA polymerase η is a limiting factor for A:T mutations in Ig genes and contributes to the antibody affinity maturation. Eur. J. Immunol. 38: 2796-2805 (2008).
11. Ehrhardt, G., Hijikata, A., Kitamura, H., Ohara, O., Wang, J.-Y., Vaughan, W. P. and Cooper, M. D. Distinctive gene expression profiles of memory B cell subpopulations in humans. J. Exp. Med. 205: 1807-1817 (2008).
12. Ouchida, R., Yamasaki, S., Hikida, M., Masuda, K., Kawamura, K., Wada, A., Mochizuki, S., Tagawa, M., Sakamoto, A., Hatano, M., Tokuhisa, T., Koseki, H., Saito, T., Kurosaki, T. and Wang, J.-Y. A Lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3ζ degradation. Immunity 29: 33-43 (2008).