IL-21 and IFN-α have both opposite and redundant role on human innate precursors and memory B-cell differentiation.

Boudigou, M.; Michee-Cospolite, M.; Hemon, P.; Grasseau, A.; Le Dantec, C.; Porchet, E.; Jamin, C.; Devauchelle, V.; Mignen, O.; Cornec, D.; Pers, J.-O.; Le Pottier, L.; Hillion, S.

doi:10.1101/2021.03.31.437810

bioRxiv · 10.1101/2021.03.31.437810

IL-21 and IFN-α have both opposite and redundant role on human innate precursors and memory B-cell differentiation.

Boudigou, M.·Michee-Cospolite, M.·Hemon, P.·Grasseau, A.·Le Dantec, C.·Porchet, E.·Jamin, C.·Devauchelle, V.·Mignen, O.·Cornec, D.·Pers, J.-O.·Le Pottier, L.·Hillion, S.

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Abstract

Immunological memory is essential for effective immune protection upon antigen rechallenge. Memory B cells encompass multiple subsets, heterogeneous in terms of phenotypes, origins and precursors, anatomical localization, and functional responses. B-cell responses are conditioned by micro-environmental signals, including cytokines. Here, we analyzed in vitro the effects of two cytokines implicated in B-cell differentiation, interferon-alpha (IFN-) and interleukin (IL)-21, on the early functional response of four different mature B-cell subsets (IgD- CD27- naive, IgD+ CD27+ unswitched, IgD- CD27+ switched and double-negative B cells). The dual response of naive and memory B cells to IL-21 allowed us to uncover a unique IgD+ CD27- CD10- B-cell population (referred to as NARB+) characterized by the expression of marginal zone B-cell markers CD45RB and CD1c. Similar to memory B cells, NARB+ cells were in a pre-activated state, allowing them to rapidly differentiate into plasmablasts upon innate signals while maintaining their susceptibility to IL-21 activation-induced apoptosis as observed for the naive compartment. Both in-depth phenotypic analysis of circulating B cells, and identification of these cells in spleen, tonsil and gut-associated lymphoid tissues, supported that NARB+ are uncommitted precursors of human marginal zone B cells.

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Boudigou, M., Michee-Cospolite, M., Hemon, P., Grasseau, A., Le Dantec, C., Porchet, E., Jamin, C., Devauchelle, V., Mignen, O., Cornec, D., Pers, J.-O., Le Pottier, L., Hillion, S.. 2021-04-01. IL-21 and IFN-α have both opposite and redundant role on human innate precursors and memory B-cell differentiation.. https://doi.org/10.1101/2021.03.31.437810

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