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Type III interferon drives thymic B cell activation and regulatory T cell generation

ABSTRACT: The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate 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 (Treg) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the Treg 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE220104 | GEO | 2023/02/13

REPOSITORIES: GEO

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Interferon dependent genes of intrathymic antigen presenting cells

Project description:The activation of thymic B cells is critical for their licensing as antigen presenting cells and resulting ability to mediate 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 (Treg) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the Treg cell repertoire. Together, these findings reveal the importance of steady state type III IFN in generating licensed thymic B cells that generate T cell tolerance to activated B cells

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