Background:

Research:

Signal for B cell differentiation
B cell receptor, membrane-bound immunoglobulin, is essential for B cell maturation as well as humoral immune response. Upon antigenic encounter, signaling processes occur through accessory signaling chains, Ig-a and Ig-b, and associated kinases. However, the results of signaling processes are very different depending on the status of B cell differentiation. Immature B cell undergoes an activation-induced cell death upon IgM crosslinking. We are currently using WEHI-231 B cells as a model of immature B cell stage cells. We showed that WEHI-231 cells had some unique signaling properties as compared to a mature B cell line. We are also performing experiments with genetically engineered mice – which have mutated genes for B cell signaling such as BTK and JNK.
In contrast, mature B cells differentiate into plasma cells or memory B cells upon stimulation through surface IgM. We are interested in the interaction between follicular dendritic cells and mature B cells. Currently, a gene for a follicular dendritic cell surface protein is cloned and we are performing studies to see what kind of functions it has and their molecular mechanisms.

Mechanism of generation of pathogenetic autoantibody
Autoimmune diseases are inflammatory disorders, which are triggered by the harmful responses of T cells, B cells, or other cells. Our laboratory is interested in the mechanism of the generation of autoantibodies in various autoimmune diseases such as rheumatoid arthritis, SLE, or atopic dermatitis. Autoantibodies could be generated through a help from specific autoreactive T cells or the provision of a strong innate immune stimulus. Using an surface plasmon resonance technique with BiaCore machine, we are performing studies to detect autoantibodies in patients’ serum. We are aiming at identifying specific B cell receptors for those autoantibodies.

Role of CD99 in lymphocyte differentiation
CD99 molecule is a 32-kDa transmembrane glycoprotein, which is highly expressed on thymocytes, memory lymphocytes, pancreatic islet cells, and primitive neuroectodermal cells. CD99 has been functionally implicated in cell migration, apoptosis, cell adhesion, Th1 cell differentiation, and intracellular transport of transmembrane proteins, but the basic molecular mechanism of CD99-mediated signal transduction is not well known. In T cells, CD99 is known as one of the costimulatory molecules for T cell receptor. Previously, we showed that CD99 engagement led to ERK activation and homotypic aggregation. We are currently performing studies to investigate the role of CD99 in lymphocyte or other immune cell differentiation.

Publications:

1. Kim HJ, Chong KH, Lee J-R, Kim J-Y, Chung DH, Hahn M-J, Kim TJ. Identification of cyclophilin A as a CD99-binding protein by the yeast two-hybrid screening. Immunol. Lett (2004) 95:155 (2004)
2. Kim HJ, Chong KH, Lee J-R, Kim J-Y, Chung DH, Hahn M-J, Kim TJ. Identification of cyclophilin A as a CD99-binding protein by the yeast two-hybrid screening. Immunol Lett (2004) on line published Aug 2nd (2004)
3. Yoon SS, Kim HJ, Chung DH, Kim TJ. CD99 costimulation up-regulates T cell receptor-mediated activation of JNK and AP-1. Mol Cells 18(2): in press (2004)
4. Kim J-Y, Lee M-H, Jeong K-I, Na H-Y, Cha H-S, Koh E-M, Kim TJ. Detection of antibodies against glucose phosphate isomerase in synovial fluid of rheumatoid arthritis using surface plasmon resonance (BIACORE) Exp Mol Med 35:310 (2003)
5. Yoon SS, Jung KI, Choi Y-L, Choi EY, Lee I-S, Park SH, Kim TJ. Engagement of CD99 triggers the exocytic transport of ganglioside GM1 and the reorganization of actin cytoskeleton. FEBS Lett 540(1-3):217 (2003)
6. Gil MC, Lee M-H, Seo J-I, Choi Y-L, Jung KC, Park SH, Kim TJ. Characterization and epitope mapping of two monoclonal antibodies against human CD99. Exp Mol Med 34(6):411 (2002)
7. Kim TJ, Cariappa A, Iacomini J, Tang M, Shih S, Bernards A, Jacks T, Pillai S. Defective proliferative responses in B lymphocytes and thymocytes that lack neurofibromin. Mol Immunol 38:701-708 (2002)
8. Yoon SS, Kim TJ. WEHI-231 cells are defective in the ligand-induced internalization of B cell antigen receptor. Immune Network 3:196-202 (2001)
9. Sohn HW, Shin YK, Lee I-S, Bae YM, Suh YH, Kim MK, Kim TJ, Jung K-C, Park WS, Park C-S, Chung DH, Ahn K, Kim IS, Ko YH, Bang YJ, Kim CW, Park SH. CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface. J Immunol 166:787-794 (2001)
10. Hahn M-J, Yoon SS, Sohn HW, Song HG, Park SH, Kim TJ. Differential activation of MAP kinase family members triggered by CD99 engagement. FEBS Letters 470:350-354 (2000)