The distinct roles of T cell-derived cytokines and a novel follicular dendritic cell-signaling molecule 8D6 in germinal center-B cell differentiation.
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.
Zhang
X
X
Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, New Orleans, LA 70121, USA.
Li
L
L
Jung
J
J
Xiang
S
S
Hollmann
C
C
Choi
Y S
YS
D019138:Antibodies, Blocking / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D020566:Dendritic Cells, Follicular / Q000502:physiology*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D006131:Growth Inhibitors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D015847:Interleukin-4