Homeostatic apoptosis prevents competition-induced atrophy in follicular B cells

Cell Rep. 2021 Jul 20;36(3):109430. doi: 10.1016/j.celrep.2021.109430.


While the intrinsic apoptosis pathway is thought to play a central role in shaping the B cell lineage, its precise role in mature B cell homeostasis remains elusive. Using mice in which mature B cells are unable to undergo apoptotic cell death, we show that apoptosis constrains follicular B (FoB) cell lifespan but plays no role in marginal zone B (MZB) cell homeostasis. In these mice, FoB cells accumulate abnormally. This intensifies intercellular competition for BAFF, resulting in a contraction of the MZB cell compartment, and reducing the growth, trafficking, and fitness of FoB cells. Diminished BAFF signaling dampens the non-canonical NF-κB pathway, undermining FoB cell growth despite the concurrent triggering of a protective p53 response. Thus, MZB and FoB cells exhibit a differential requirement for the intrinsic apoptosis pathway. Homeostatic apoptosis constrains the size of the FoB cell compartment, thereby preventing competition-induced FoB cell atrophy.

Keywords: BAFF; NF-κB; cell growth; cellular lifespan; follicular B cells; intercellular competition; intrinsic apoptosis; marginal zone B cells; mature B cell homeostasis; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Apoptosis*
  • Atrophy
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / pathology*
  • Cell Count
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cell Size
  • Cell Survival / genetics
  • Cellular Senescence / genetics
  • Gene Deletion
  • Gene Expression Regulation
  • Homeostasis*
  • Mice, Knockout
  • Sequence Analysis, RNA
  • Thymus Gland / immunology
  • Transcription Factors / metabolism
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism


  • B-Cell Activating Factor
  • Tnfsf13b protein, mouse
  • Transcription Factors
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein