A self-sustaining layer of early-life-origin B cells drives steady-state IgA responses in the adult gut

• DOI: 10.1016/j.immuni.2022.08.018
• Publication Date: 2022-09-16T14:48:31Z
• Authors: Stefano Vergani; Konjit Getachew M...; Clément Da Silva; Alexander Doyle; Trine Ahn Kristia...; Selene Sodini; Niklas Krausse; Giorgia Montano; Knut Kotarsky; Joy Nakawesi; Hugo Åkerstrand; Stijn Vanhee; Sneh Lata Gupta; David Bryder; William Winston A...; Katharina Lahl; Joan Yuan
• Keywords: EXPRESSION; B-Lymphocytes; POSITIVE SELECTION; BONE-MARROW; Microbiota; Immunology; Plasma Cells; INNATE; IMMUNITY; Germinal Center; Immunoglobulin A; Mice; 03 medical and health sciences; Infectious Diseases; 0302 clinical medicine; PLASMA-CELLS; Medicine and Health Sciences; Immunology and Allergy; Animals; MARGINAL ZONE; ROTAVIRUS INFECTION; IN-VIVO; COMMENSAL-BACTERIA

The adult immune system consists of cells that emerged at various times during ontogeny. We aimed to define the relationship between developmental origin and composition of the adult B cell pool during unperturbed hematopoiesis. Lineage tracing stratified murine adult B cells based on the timing of output, revealing that a substantial portion originated within a restricted neonatal window. In addition to B-1a cells, early-life time-stamped B cells included clonally interrelated IgA plasma cells in the gut and bone marrow. These were actively maintained by B cell memory within gut chronic germinal centers and contained commensal microbiota reactivity. Neonatal rotavirus infection recruited recurrent IgA clones that were distinct from those arising by infection with the same antigen in adults. Finally, gut IgA plasma cells arose from the same hematopoietic progenitors as B-1a cells during ontogeny. Thus, a complex layer of neonatally imprinted B cells confer unique antibody responses later in life.