| First Author | Misawa T | Year | 2020 |
| Journal | Sci Immunol | Volume | 5 |
| Issue | 43 | PubMed ID | 31980486 |
| Mgi Jnum | J:296761 | Mgi Id | MGI:6469779 |
| Doi | 10.1126/sciimmunol.aaz0085 | Citation | Misawa T, et al. (2020) Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation. Sci Immunol 5(43) |
| abstractText | T follicular helper cells (TFH) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in Prkd2, encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies in mice with a targeted null mutation of Prkd2 demonstrated polyclonal hypergammaglobulinemia of IgE, IgG1, and IgA isotypes, which was exacerbated by the T cell-dependent humoral response to immunization. GC formation and GC B cells were increased in Prkd2(-/-) spleens. These effects were the result of excessive cell-autonomous TFH development caused by unrestricted Bcl6 nuclear translocation in Prkd2(-/-) CD4(+) T cells. Prkd2 directly binds to Bcl6, and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development. In response to immunization, Bcl6 repressed Prkd2 expression in CD4(+) T cells, thereby committing them to TFH development. Thus, Prkd2 and Bcl6 form a mutually inhibitory positive feedback loop that controls the stable transition from naive CD4(+) T cells to TFH during the adaptive immune response. |
