Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection

Perugino, C.; Liu, H.; Feldman, J.; Marbourg, J.; Guy, T.; Hui, A.; Ingram, N.; Liebaert, J.; Chaudhary, N.; Tao, W.; Jacob-Dolan, C.; Hauser, B. M.; Mian, Z.; Nathan, A.; Zhao, Z.; Kaseke, C.; Tano-Menka, R.; Getz, M.; Senjobe, F.; Berrios, C.; Ofoman, O.; Manickas-Hill, Z.; Wesemann, D.; Lemieux, J.; Goldberg, M. B.; Nundel, K.; Moormann, A. M.; Marshak-Rothstein, A.; Larocque, R.; Ryan, E.; Iafrate, A. J.; Lingwood, D.; Gaiha, G.; Charles, R.; Balazs, A. B.; Pandit, A.; Naranbhai, V.; Schmidt, A.; Pillai, S.

doi:10.1101/2024.11.29.624972

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bioRxiv · 10.1101/2024.11.29.624972

Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection

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Abstract

Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized in terms of durability. The relative durability of eight non-overlapping human B cell sub-populations covering 100% of all human class-switched B cells was interrogated. Only two long-lived B cell populations persisted in the relative absence of antigen. In addition to canonical germinal center-derived switched-memory B cells with an IgD-CD27+ CXCR5+ phenotype, a second, non-canonical, but distinct memory population of IgD-CD27- CXCR5+ DN1 B cells was also durable, exhibited a unique TP63-linked transcriptional and anti-apoptotic signature, had low levels of somatic hypermutation, but was more clonally expanded than canonical switched-memory B cells. DN1 B cells likely evolved to preserve immunological breadth and may represent the human counterparts of rodent extrafollicular memory B cells that, unlike canonical memory B cells, can enter germinal centers and facilitate B cell and antibody evolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/624972v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@169c77forg.highwire.dtl.DTLVardef@1a872f5org.highwire.dtl.DTLVardef@1360cforg.highwire.dtl.DTLVardef@38d7ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Perugino, C., Liu, H., Feldman, J., Marbourg, J., Guy, T., Hui, A., Ingram, N., Liebaert, J., Chaudhary, N., Tao, W., Jacob-Dolan, C., Hauser, B. M., Mian, Z., Nathan, A., Zhao, Z., Kaseke, C., Tano-Menka, R., Getz, M., Senjobe, F., Berrios, C., Ofoman, O., Manickas-Hill, Z., Wesemann, D., Lemieux, J., Goldberg, M. B., Nundel, K., Moormann, A. M., Marshak-Rothstein, A., Larocque, R., Ryan, E., Iafrate, A. J., Lingwood, D., Gaiha, G., Charles, R., Balazs, A. B., Pandit, A., Naranbhai, V., Schmidt, A., Pillai, S.. 2024-12-04. Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection. https://doi.org/10.1101/2024.11.29.624972

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