The strength of BCR signaling shapes terminal development of follicular helper T cells in mice |
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Authors: | Antoine Sacquin Mylène Gador Nicolas Fazilleau |
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Affiliation: | 1. Centre de Physiopathologie de Toulouse Purpan, Toulouse, France;2. INSERM, Toulouse, France;3. CNRS, Toulouse, France;4. Université Toulouse III Paul‐Sabatier, Toulouse, France |
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Abstract: | Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell‐Tfh cell interactions result either in an extra‐follicular low affinity B‐cell response or in germinal center reactions producing high‐affinity memory B cells and long‐lived plasma cells. As Tfh cells influence B‐cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh‐cell differentiation in vitro, which correlated with decreased expression of ICOS‐L at the surface of stimulated B cells. Further, we comprehensively demonstrated that ICOS‐L expression correlated with the level of Tfh differentiation irrespective of antigen presentation at the surface of activated B cells. Our in vivo experiments could show that immunization with a high‐affinity antigen for B cells resulted in much less Tfh development than immunization with low‐affinity antigen. Furthermore, blocking ICOS‐L in vivo inhibited Tfh development when using low‐affinity antigen. Altogether, these results indicate that BCR affinity shapes Tfh‐cell development in part through ICOS/ICOS‐L interactions. Ultimately, we reveal new depths in the B cell‐Tfh cell crosstalk that could eventually result in better vaccine protocols. |
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Keywords: | Antigen receptors B cells BCR Follicular helper T cells ICOS‐L Immune responses |
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