| First Author | Lanahan SM | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 8 | Pages | 1422-1431 |
| PubMed ID | 38961274 | Mgi Jnum | J:362449 |
| Mgi Id | MGI:7859575 | Doi | 10.1038/s41590-024-01890-1 |
| Citation | Lanahan SM, et al. (2024) PI3Kgamma in B cells promotes antibody responses and generation of antibody-secreting cells. Nat Immunol 25(8):1422-1431 |
| abstractText | The differentiation of naive and memory B cells into antibody-secreting cells (ASCs) is a key feature of adaptive immunity. The requirement for phosphoinositide 3-kinase-delta (PI3Kdelta) to support B cell biology has been investigated intensively; however, specific functions of the related phosphoinositide 3-kinase-gamma (PI3Kgamma) complex in B lineage cells have not. In the present study, we report that PI3Kgamma promotes robust antibody responses induced by T cell-dependent antigens. The inborn error of immunity caused by human deficiency in PI3Kgamma results in broad humoral defects, prompting our investigation of roles for this kinase in antibody responses. Using mouse immunization models, we found that PI3Kgamma functions cell intrinsically within activated B cells in a kinase activity-dependent manner to transduce signals required for the transcriptional program supporting differentiation of ASCs. Furthermore, ASC fate choice coincides with upregulation of PIK3CG expression and is impaired in the context of PI3Kgamma disruption in naive B cells on in vitro CD40-/cytokine-driven activation, in memory B cells on toll-like receptor activation, or in human tonsillar organoids. Taken together, our study uncovers a fundamental role for PI3Kgamma in supporting humoral immunity by integrating signals instructing commitment to the ASC fate. |
