The Francis Crick Institute
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Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

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journal contribution
posted on 2020-09-07, 11:19 authored by Julia Merkenschlager, Mickaël J Ploquin, Urszula Eksmond, Rakieb Andargachew, Georgina Thorborn, Andrew Filby, Marion Pepper, Brian Evavold, George Kassiotis
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.