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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.

Original publication

DOI

10.4049/jimmunol.1001730

Type

Journal article

Journal

J Immunol

Publication Date

01/10/2010

Volume

185

Pages

4042 - 4052

Keywords

Adoptive Transfer, Animals, Antibody Formation, B-Lymphocytes, Blotting, Western, Cell Separation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Germinal Center, Lymphocyte Activation, Mice, Mice, Transgenic, Microscopy, Fluorescence, Phosphatidylinositol 3-Kinases, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, Helper-Inducer