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

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.

The BAFF-APRIL System in Cancer

“…The evidence of the effect of the BAFF-APRIL system on other immune cells is minimal. Pre-clinical work suggests that BAFF-BAFF-R signaling is critical for maintaining the splenic NK cell population at a steady state but is dispensable for NK cell maturation [ 94 ]. NK cells do not express BAFF receptors, neither at steady state nor in autoimmune conditions.…”

The Spectrum of Extraglandular Manifestations in Primary Sjögren’s Syndrome

“…In the salivary glands of pSS patients, subsets of unconventional NK cells that may produce inflammatory cytokines such as IL-22 were identified [ 59 ]. In addition, NK cells can facilitate BAFF production [ 60 ]. Furthermore, in pSS patients with EGMs, a higher number of NK cells was detected, implying their role in clinically aggressive disease [ 61 ].…”

The effect of immune cell traits on efficacy and adverse drug reactions of platinum drugs： A Mendelian randomization analysis

“…It was found that the expression levels of BAFF-R and TACI transcripts did not change signi cantly, but the transcription level of BCMA increased. When studying the relationship between BAFF and NK cells in the occurrence and progress of systemic lupus erythematosus, Quah PS et al found that BAFF signal is very important to maintain the number of NK cells in spleen through BAFF-R. BAFF has an indirect effect on NK cell homeostasis, but has no effect on NK cell function (Quah et al 2022). Rong HM team intend to explore the metabolic effects of BAFF-R on Pneumocystis pneumonia (PCP) (Rong et al 2023).…”