Cross-linking of MHC class II molecules interferes with phorbol 12,13-dibutyrate-induced differentiation of resting B cells by inhibiting Rac-associated ROS-dependent ERK/p38 MAP kinase pathways leading to NF-kappaB activation.
In addition to their essential role in antigen presentation, major histocompatibility complex (MHC) class II molecules have been described as the receptor associated with signal transduction regulating B-cell function. In previous experiments, we found that cross-linking of MHC class II molecules with corresponding anti-MHC class II antibodies inhibited NF-kappaB-activated signaling pathways associated with the proliferation and differentiation of the LPS-stimulated primary and resting B-cell line, 38B9. We also found that exposure to the anti-MHC class II antibody reduced the production of ROS, which function as secondary signal transducers, in the phorbol 12,13-dibutyrate (PDBU)-treated (but not in the LPS-treated) resting B-cell line. In this study, we investigated the molecular mechanisms in the ROS-associated signaling pathway leading to PDBU-induced NF-kappaB activation that results in B-cell differentiation and speculated that the signaling pathway was inhibited by exposure to the anti-MHC class II antibody. We also found that this inhibition was mediated through down-regulation of the activated Rac/ROS-associated ERK/p38 MAPK signaling pathway in PDBU-treated 38B9 cells. Collectively, these findings suggest that ROS-associated molecules are involved in MHC class II-associated negative signal transduction in resting B cells.
Yang
Hee-Young
HY
Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju 561-756, Republic of Korea.
Kim
Ju
J
Chung
Gook-Hyun
GH
Lee
Jeong-Chae
JC
Jang
Yong-Suk
YS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D015240:Phorbol 12,13-Dibutyrate; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins