Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction - PubMed (original) (raw)

. 2010 Oct 1;185(7):4042-52.

doi: 10.4049/jimmunol.1001730. Epub 2010 Sep 8.

Sarah E Bell, Dorottya Kovesdi, Michelle L Janas, Dalya R Soond, Louise M C Webb, Sara Santinelli, Ted Saunders, Barbara Hebeis, Nigel Killeen, Klaus Okkenhaug, Martin Turner

Affiliations

Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction

Julia Rolf et al. J Immunol. 2010.

Abstract

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 p110δ catalytic subunit of the PI3K pathway, we established that p110δ 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 p110δ in T cells. Furthermore, by deleting phosphatase and tensin homolog deleted on chromosome 10, which opposes p110δ 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. P110δ was not required for the expression of B cell lymphoma 6, the downregulation of CCR7, or T cell entry into primary follicles. Instead, p110δ 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.

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