| First Author | Nashar TO | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 2 | Pages | 827-38 |
| PubMed ID | 16393966 | Mgi Jnum | J:126597 |
| Mgi Id | MGI:3761728 | Doi | 10.4049/jimmunol.176.2.827 |
| Citation | Nashar TO, et al. (2006) Dynamics of MHC class II-activating signals in murine resting B cells. J Immunol 176(2):827-38 |
| abstractText | MHC class II (MHC II) proteins are competent signaling molecules on APC. However, little is known about the mechanisms that control generation of their activating signals. Previous reports highlighted a number of factors that could affect the nature and outcome of MHC II signals, including the inability of MHC II ligation on resting vs activated murine B cells to induce mobilization of Ca2+. In the present study, we report that ligation of MHC II on resting murine B cells reproducibly induces mobilization of intracellular Ca2+ using both mAbs and cognate T cells as ligands. Mobilization of Ca2+ was independent of MHC II haplotype, isotype, or mouse genetic background. MHC II-mediated mobilization of Ca2+ is completely inhibited by inhibitors of src-like kinases and syk, and MHC II ligation increases overall tyrosine phosphorylation level. Moreover, MHC II ligation results in specific up-regulation of CD86. However, induction of these responses is dependent on the type of anti-MHC II Ab used, suggesting that epitope specificity and/or the nature of ligation is important. Moreover, we demonstrate that MHC II-derived signals are strictly regulated by the order and timing of BCR and CD40 signals, suggesting coordination of these signals preserves the integrity of early B cell priming events. Thus, the mode and the context of MHC II ligation influence generation of MHC II-derived activating signals in resting B cells. Based on these results, a new model that highlights the role of MHC II-activating signals in regulation of Ag presentation by B cells is proposed. |
