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

Stefano Vergani, Konjit Getachew Muleta, Clément Da Silva, Alexander Doyle, Trine Ahn Kristiansen, Selene Sodini, Niklas Krausse, Giorgia Montano, Knut Kotarsky, Joy Nakawesi, Hugo Åkerstrand, Stijn Vanhee, Sneh Lata Gupta, David Bryder, William Winston Agace, Katharina Lahl, Joan Yuan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1829-1842.e6
Issue number10
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Immunology
  • Immunology in the medical area

Free keywords

  • B cell memory
  • B-1 cells
  • early-life exposure
  • early-life-origin B cells
  • gut B cells
  • IgA
  • plasma cells
  • rotavirus
  • time-stamping
  • window of opportunity


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