| First Author | Wray-Dutra MN | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 10 | Pages | 2485-2496 |
| PubMed ID | 30194267 | Mgi Jnum | J:270222 |
| Mgi Id | MGI:6203427 | Doi | 10.1084/jem.20180617 |
| Citation | Wray-Dutra MN, et al. (2018) Activated PIK3CD drives innate B cell expansion yet limits B cell-intrinsic immune responses. J Exp Med 215(10):2485-2496 |
| abstractText | Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell-specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell-independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell-dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell-intrinsic contributions to the APDS phenotype. |
