Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455.
Research Informatics Solutions, Laboratory Medicine and Pathology Group, Minnesota Supercomputing Institute, Minneapolis, MN 55455.
Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2220120120. doi: 10.1073/pnas.2220120120. Epub 2023 Feb 21.
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) development. Finally, from TCR deep sequencing, we estimate that licensed B cells induce development of a substantial fraction of the T 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.
胸腺 B 细胞的激活对于其作为抗原呈递细胞的许可和由此产生的介导 T 细胞中枢耐受的能力至关重要。导致许可的过程仍不完全清楚。通过将胸腺 B 细胞与稳定状态下的激活派尔集合淋巴结 B 细胞进行比较，我们发现胸腺 B 细胞的激活始于新生儿期，其特征是 TCR/CD40 依赖性激活，随后发生免疫球蛋白类别转换重组（CSR），而不形成生发中心。转录分析还表明存在强烈的干扰素特征，而在外周组织中则不明显。胸腺 B 细胞的激活和 CSR 主要依赖于 III 型 IFN 信号，而胸腺 B 细胞中 III 型 IFN 受体的缺失导致调节性 T 细胞（T）发育减少。最后，从 TCR 深度测序中，我们估计许可的 B 细胞诱导了大量 T 细胞库的发育。总之，这些发现揭示了稳态 III 型 IFN 在产生诱导 T 细胞对激活 B 细胞耐受的许可性胸腺 B 细胞中的重要性。
