Journal article

Homeostatic apoptosis prevents competition-induced atrophy in follicular B cells

Stephane Chappaz, Kate McArthur, Liam Kealy, Charity W Law, Maximilien Tailler, Rachael M Lane, Anna Lieschke, Matthew E Ritchie, Kim L Good-Jacobson, Andreas Strasser, Benjamin T Kile

CELL REPORTS | CELL PRESS | Published : 2021

Abstract

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..

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Grants

Awarded by Australian Federal Government Postgraduate Award


Awarded by Independent Research Institutes Infrastructure Support Scheme Grant from the Australian National Health and Medical Research Council


Awarded by SCOR grant from the Leukemia and Lymphoma Society (US)


Funding Acknowledgements

We thank S. Nutt and S. Willis for Spib<SUP>-/-</SUP> mice, F. Mackay for BAFF Tg and Tnfrsf13c<SUP>-/-</SUP> mice, and U. Siebenlist for Nfkb2<SUP>-/-</SUP> mice. We thank the WEHI Bioservices staff for mouse work and are grateful to T. Saunders for critically reviewing the manuscript. This work was supported by an Australian Federal Government Postgraduate Award (to K.M.); Project Grants (1077750 and 1106471), Program Grants (1016647, 1113577, and 101671), and Fellowships (1063008 to B.T.K., 1020363 to A.S., and 1161352 to K.M.); Bellberry-Viertel Senior Medical Research Fellowship (to K.L.G.-J.); an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council; the Australian Cancer Research Fund; a SCOR grant (7001-13) from the Leukemia and Lymphoma Society (US); and a Victorian State Government Operational Infrastructure Support Grant.