Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
journal contributionposted on 07.09.2020 by Julia Merkenschlager, Mickaël J Ploquin, Urszula Eksmond, Rakieb Andargachew, Georgina Thorborn, Andrew Filby, Marion Pepper, Brian Evavold, George Kassiotis
Any type of content formally published in an academic journal, usually following a peer-review process.
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.