Antigen affinity and site of immunization dictate B cell recall responses

Termote, M.; Marques, R. C.; Hyllner, E.; Guryleva, M. V.; Henskens, M.; Brutscher, A.; Baken, I. J. L.; Castro Dopico, X.; Dalmau Gasull, A.; Murrell, B.; Stamatatos, L.; Westerberg, L. S.; Dosenovic, P.

doi:10.1101/2024.04.19.590239

bioRxiv · 10.1101/2024.04.19.590239

Antigen affinity and site of immunization dictate B cell recall responses

Termote, M.·Marques, R. C.·Hyllner, E.·Guryleva, M. V.·Henskens, M.·Brutscher, A.·Baken, I. J. L.·Castro Dopico, X.·Dalmau Gasull, A.·Murrell, B.·Stamatatos, L.·Westerberg, L. S.·Dosenovic, P.

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Abstract

Protective antibodies against HIV-1 require unusually high levels of somatic hypermutations (SHMs) introduced in germinal centers (GCs). To achieve this, a sequential vaccination approach was proposed. Using HIV-1 antibody knock-in mice with fate-mapping genes, we examined if antigen affinity affects the outcome of the B cell recall response. Compared to high affinity boost, low affinity boost resulted in decreased numbers of memory-derived B cells in secondary GCs, but with higher average SHM, indicating an affinity threshold for memory B cells to enter secondary GCs. Upon boosting local LNs, numbers of residual GC B cells increased independent on antigen affinity, while average SHM decreased. Our results demonstrate that antigen affinity and location of the boost affect the outcome of the B cell recall response. These results can help guide the design of vaccine immunogens aiming to selectively engage specific B cell clones for further SHM diversification.

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Termote, M., Marques, R. C., Hyllner, E., Guryleva, M. V., Henskens, M., Brutscher, A., Baken, I. J. L., Castro Dopico, X., Dalmau Gasull, A., Murrell, B., Stamatatos, L., Westerberg, L. S., Dosenovic, P.. 2024-04-23. Antigen affinity and site of immunization dictate B cell recall responses. https://doi.org/10.1101/2024.04.19.590239

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