The Distinct Roles of T Cell-Derived Cytokines and a Novel Follicular Dendritic Cell-Signaling Molecule 8D6 in Germinal Center-B Cell Differentiation

• Published in: The Journal of immunology (1950) Vol. 167; no. 1; pp. 49 - 56
• Main Authors: Zhang, Xin, Li, Li, Jung, Jaeho, Xiang, Shulin, Hollmann, Christiane, Choi, Yong Sung
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.07.2001
• Subjects: Antibodies, Blocking - physiology; Antibodies, Monoclonal - physiology; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - physiology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Division - immunology; Cell Line; Cells, Cultured; Coculture Techniques; Cytokines - biosynthesis; Cytokines - physiology; Dendritic Cells, Follicular - physiology; Germinal Center - cytology; Germinal Center - immunology; Growth Inhibitors - physiology; Humans; Immunologic Memory; Interleukin-10 - physiology; Interleukin-4 - physiology; Plasma Cells - cytology; Plasma Cells - immunology; Signal Transduction - immunology; Stem Cells - cytology; Stem Cells - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.1.49

Germinal center-B (GC-B) cells differentiate into memory B cells and plasma cells (PC) through interaction with T cells and follicular dendritic cells (FDC). Activated T cell and FDC play distinct roles in this process. The detailed kinetic experiments revealed that cytokines secreted by activated T cells determined the pathway of GC-B cell differentiation. IL-4 directs GC-B cells to differentiate into memory B cells, whereas IL-10 steers them into PC. FDC/HK cells do not direct either pathway, but provide signals for proliferation of GC-B cells. A novel FDC-signaling molecule 8D6 (FDC-SM-8D6) produced by FDC augments PC generation in the GC. FDC-SM-8D6-specific mAb blocked PC generation and IgG secretion but not memory B cell proliferation. COS cells expressing FDC-SM-8D6 enhanced GC-B cell proliferation and Ab secretion, which was blocked by mAb 8D6. In the cultures with B cell subsets, PC generation was inhibited by mAb 8D6 in the cultures with CD27(+) B cells but not in the culture with CD27(-) B cells, suggesting that CD27(+) PC precursor is the specific target of FDC-SM-8D6 stimulation.