MHC class II molecules activate NFAT and the ERK group of MAPK through distinct signaling pathways in B cells.
MHC class II (MHC-II) molecules are capable of transducing signals with the help of associated molecules. Although the search to find associated molecules over the past few years has been fruitful, it remains clear that not all signaling components and their mechanisms of action have been identified. In this study, we investigated calcium and MAPK signaling pathways using the BJAB and Raji human B cell lines. We demonstrate that calcium mobilization is an isotype-independent event that triggers the dephosphorylation of NFAT. We also show that BCR activation followed by MHC-II ligation increases the activation of NFAT. This signaling pathway differs from MHC-II-mediated MAP activation, where MEK1/2 and ERK1/2 phosphorylation are isotype-specific events, which correspond to the induction of c-Fos and formation of AP-1. Future studies should elucidate the intertwined, intricate signaling cascades triggered by BCR and MHC-II leading to humoral immune responses.
Haylett
Romney S
RS
Institute of Immunology, RWTH Aachen University, Germany.
Koch
Norbert
N
Rink
Lothar
L
D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D006682:HLA-DP Antigens / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium