1. IL-21 and IFN-alpha have both opposite and redundant role on human innate precursors and memory B-cell differentiation
- Author
-
Marina Boudigou, Magalie Michée-Cospolite, Patrice Hémon, Alexis Grasseau, Christelle Le Dantec, Emmanuelle Porchet, Christophe Jamin, Valérie Devauchelle, Olivier Mignen, Divi Cornec, Jacques-Olivier Pers, Laëtitia Le Pottier, and Sophie Hillion
- Subjects
education.field_of_study ,biology ,Population ,Interleukin ,Spleen ,Marginal zone ,Immunoglobulin D ,In vitro ,Cell biology ,medicine.anatomical_structure ,Antigen ,Apoptosis ,biology.protein ,medicine ,education - 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-α) 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.
- Published
- 2021