Homeostatic apoptosis prevents competition-induced atrophy in follicular B cells
- Chappaz, S; McArthur, K; Kealy, L; Law, CW; Tailler, M; Lane, RM; Lieschke, A; Ritchie, ME; Good-Jacobson, KL; Strasser, A; Kile, BT;
Publication Year 2021-07-20, Volume 36, Issue #3, Page 109430
- Journal Title
- Cell Reports
- 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.
- Baff; Nf-κb; cell growth; cellular lifespan; follicular B cells; intercellular competition; intrinsic apoptosis; marginal zone B cells; mature B cell homeostasis; p53
- WEHI Research Division(s)
- Epigenetics And Development; Blood Cells And Blood Cancer
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-08-16 10:40:35Last Modified: 2021-08-16 10:49:37