Developmental changes in the rules for B cell selection*

Research output: Contribution to journalReview articlepeer-review


The autoimmune checkpoint during B cell maturation eliminates self-antigen reactive specificities from the mature B cell repertoire. However, an exception to this rule is illustrated by B-1 cells, an innate-like self-reactive B cell subset that is positively selected into the mature B cell pool in a self-antigen-driven fashion. The mechanisms by which B-1 cells escape central tolerance have puzzled the field for decades. A key clue comes from their restricted developmental window during fetal and neonatal life. Here we use B-1 cells as a prototypic early life derived B cell subset to explore developmental changes in the constraints of B cell selection. We discuss recent advancements in the understanding of the molecular program, centered around the RNA binding protein Lin28b, that licenses self-reactive B-1 cell output during ontogeny. Finally, we speculate on the possible link between the unique rules of early life B cell tolerance and the establishment of B cell – microbial mutualism to propose an integrated model for how developmental and environmental cues come together to create a protective layer of B cell memory involved in neonatal immune imprinting.

Original languageEnglish
Pages (from-to)194-202
JournalImmunological Reviews
Issue number1
Early online date2021 Jan 26
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Immunology in the medical area
  • Cell and Molecular Biology

Free keywords

  • B cell tolerance
  • B-1 cells
  • early life B cell memory
  • Lin28b
  • neonatal immune imprinting
  • window of opportunity


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