First Author | Merkenschlager J | Year | 2016 |
Journal | Nat Commun | Volume | 7 |
Pages | 10281 | PubMed ID | 26728651 |
Mgi Jnum | J:235821 | Mgi Id | MGI:5803757 |
Doi | 10.1038/ncomms10281 | Citation | Merkenschlager J, et al. (2016) Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response. Nat Commun 7:10281 |
abstractText | Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4(+) T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4(+) T-cell response also to vaccination or tumour challenge, revealing a common effect. |