| First Author | Martinez RJ | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 9 | Pages | e2220120120 |
| PubMed ID | 36802427 | Mgi Jnum | J:348478 |
| Mgi Id | MGI:7521930 | Doi | 10.1073/pnas.2220120120 |
| Citation | Martinez RJ, et al. (2023) Type III interferon drives thymic B cell activation and regulatory T cell generation. Proc Natl Acad Sci U S A 120(9):e2220120120 |
| abstractText | The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate T cell central tolerance. The processes leading to licensing are still not fully understood. By comparing thymic B cells to activated Peyer's patch B cells at steady state, we found that thymic B cell activation starts during the neonatal period and is characterized by TCR/CD40-dependent activation, followed by immunoglobulin class switch recombination (CSR) without forming germinal centers. Transcriptional analysis also demonstrated a strong interferon signature, which was not apparent in the periphery. Thymic B cell activation and CSR were primarily dependent on type III IFN signaling, and loss of type III IFN receptor in thymic B cells resulted in reduced thymocyte regulatory T cell (T(reg)) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the T(reg) cell repertoire. Together, these findings reveal the importance of steady-state type III IFN in generating licensed thymic B cells that induce T cell tolerance to activated B cells. |
