The effects of B-cell-activating factor on the population size, maturation and function of murine natural killer cells

Pin Shie Quah; Vivien Sutton; Eden Whitlock; William A Figgett; Daniel M Andrews; Kirsten A Fairfax; Fabienne Mackay

doi:10.1111/imcb.12585

The effects of B-cell-activating factor on the population size, maturation and function of murine natural killer cells

Immunol Cell Biol. 2022 Nov;100(10):761-776. doi: 10.1111/imcb.12585. Epub 2022 Oct 8.

Authors

Pin Shie Quah^{1

2}, Vivien Sutton^{3

4}, Eden Whitlock^{2

5}, William A Figgett^{1

2

6}, Daniel M Andrews^{1

7}, Kirsten A Fairfax^#^{8

9

10}, Fabienne Mackay^#^{1

2

5

11}

Affiliations

¹ Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia.
² Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
³ Rosie Lew Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁴ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
⁵ QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
⁶ Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁷ Bioproperties, Ringwood, Melbourne, VIC, Australia.
⁸ Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁹ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
¹⁰ School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
¹¹ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.

^# Contributed equally.

Abstract

The role of B-cell-activating factor (BAFF) in B-lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild-type (WT), BAFF^-/- (BAFF deficient), BAFF-R^-/- (BAFF receptor deficient), TACI^-/- (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA^-/- (B-cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF-R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF^-/- and BAFF Tg mice produced interferon-γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.

Keywords: Autoimmunity; Cancer; Immunodeficiency; Innate immunity; Natural killer cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Interleukin-4
Killer Cells, Natural / metabolism
Lupus Erythematosus, Systemic*
Mice
Mice, Transgenic
Population Density
Transmembrane Activator and CAML Interactor Protein* / genetics

Substances

Transmembrane Activator and CAML Interactor Protein
Interleukin-4