| First Author | Rolf J | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 7 | Pages | 4042-52 |
| PubMed ID | 20826752 | Mgi Jnum | J:164283 |
| Mgi Id | MGI:4831054 | Doi | 10.4049/jimmunol.1001730 |
| Citation | Rolf J, et al. (2010) Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction. J Immunol 185(7):4042-52 |
| abstractText | The generation of high-affinity Abs is essential for immunity and requires collaboration between B and T cells within germinal centers (GCs). By using novel mouse models with a conditional deletion of the p110delta catalytic subunit of the PI3K pathway, we established that p110delta is required in T cells, but not in B cells, for the GC reaction. We found the formation of T follicular helper (T(FH)) cells to be critically dependent on p110delta in T cells. Furthermore, by deleting phosphatase and tensin homolog deleted on chromosome 10, which opposes p110delta in activated T cells, we found a positive correlation between increased numbers of T(FH) cells and GC B cells. These results are consistent with the hypothesis that T cell help is the limiting factor in the GC reaction. P110delta was not required for the expression of B cell lymphoma 6, the downregulation of CCR7, or T cell entry into primary follicles. Instead, p110delta was the critical catalytic subunit for ICOS downstream signaling and the production of key T(FH) cytokines and effector molecules. Our findings support a model in which the magnitude of the GC reaction is controlled by the activity of the PI3K pathway in T(FH) cells. |
