| First Author | Merkenschlager J | Year | 2021 |
| Journal | Nature | Volume | 591 |
| Issue | 7850 | Pages | 458-463 |
| PubMed ID | 33536617 | Mgi Jnum | J:307320 |
| Mgi Id | MGI:6710167 | Doi | 10.1038/s41586-021-03187-x |
| Citation | Merkenschlager J, et al. (2021) Dynamic regulation of TFH selection during the germinal centre reaction. Nature 591(7850):458-463 |
| abstractText | The germinal centre is a dynamic microenvironment in which B cells that express high-affinity antibody variants produced by somatic hypermutation are selected for clonal expansion by limiting the numbers of T follicular helper cells(1,2). Although much is known about the mechanisms that control the selection of B cells in the germinal centre, far less is understood about the clonal behaviour of the T follicular helper cells that help to regulate this process. Here we report on the dynamic behaviour of T follicular helper cell clones during the germinal centre reaction. We find that, similar to germinal centre B cells, T follicular helper cells undergo antigen-dependent selection throughout the germinal centre reaction that results in differential proliferative expansion and contraction. Increasing the amount of antigen presented in the germinal centre leads to increased division of T follicular helper cells. Competition between T follicular helper cell clones is mediated by the affinity of T cell receptors for peptide-major-histocompatibility-complex ligands. T cells that preferentially expand in the germinal centre show increased expression of genes downstream of the T cell receptor, such as those required for metabolic reprogramming, cell division and cytokine production. These dynamic changes lead to marked remodelling of the functional T follicular helper cell repertoire during the germinal centre reaction. |
