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Summary: B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing. Inhibition of ADAM10 augments BAFF-dependent survival of primary human B cells, whereas inhibition of ADAM17 increases BAFFR expression levels on germinal center B cells. Therefore, BAFF-induced processing of BAFFR regulates BAFF-mediated B cell responses in a TACI-dependent manner. : Smulski et al. report that the B cell survival receptor BAFFR undergoes ligand-induced shedding but only in cells co-expressing a second receptor for BAFF called TACI. BAFFR shedding can be performed by ADAM10 in circulating B cells or by ADAM17 in germinal center B cells and limits BAFF-mediated survival signals. Keywords: B cell, BAFF-receptor, BAFFR, TACI, ADAM10, ADAM17, metalloprotease, processing, ectodomain shedding, germinal center, survival

Waxes are critical in limiting non-stomatal water loss in higher terrestrial plants by making up the limiting barrier for water diffusion across cuticles. Using a differential extraction protocol, we investigated the influence of various wax fractions on the cuticular transpiration barrier. Triterpenoids (TRPs) and very long-chain aliphatics (VLCAs) were selectively extracted from isolated adaxial leaf cuticles using methanol (MeOH) followed by chloroform (TCM). The water permeabilities of the native and the solvent-treated cuticles were measured gravimetrically. Seven plant species ( Camellia sinensis , Ficus elastica , Hedera helix , Ilex aquifolium , Nerium oleander , Vinca minor, and Zamioculcas zamiifolia ) with highly varying wax compositions ranging from nearly pure VLCA- to TRP-dominated waxes were selected. After TRP removal with MeOH, water permeability did not or only slightly increase. The subsequent VLCA extraction with TCM led to increases in cuticular water permeabilities by up to two orders of magnitude. These effects were consistent across all species investigated, providing direct evidence that the cuticular transpiration barrier is mainly composed of VLCA. In contrast, TRPs play no or only a minor role in controlling water loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seufert, Staiger, Arand, Bueno, Burghardt and Riederer.)

Background and Aims: The cuticle of a limited number of plant species contains cutan, a chemically highly resistant biopolymer. As yet, the biosynthesis of cutan is not fully understood. Attempting to further unravel the origin of cutan, we analysed the chemical composition of enzymatically isolated cuticular membranes of Agave americana leaves., Methods: Cuticular waxes were extracted with organic solvents. Subsequently, the dewaxed cuticular membrane was depolymerized by acid-catalysed transesterification yielding cutin monomers and cutan, a non-hydrolysable, cuticular membrane residue. The cutan matrix was analysed by thermal extraction, flash pyrolysis and thermally assisted hydrolysis and methylation to elucidate the monomeric composition and deduce a putative biosynthetic origin., Key Results: According to gas chromatography-mass spectrometry analyses, the cuticular waxes of A. americana contained primarily very-long-chain alkanoic acids and primary alkanols dominated by C32, whereas the cutin biopolyester of A. americana mainly consisted of 9,10-epoxy ω-hydroxy and 9,10,ω-trihydroxy C18 alkanoic acids. The main aliphatic cutan monomers were alkanoic acids, primary alkanols, ω-hydroxy alkanoic acids and alkane-α,ω-diols ranging predominantly from C28 to C34 and maximizing at C32. Minor contributions of benzene-1,3,5-triol and derivatives suggested that these aromatic moieties form the polymeric core of cutan, to which the aliphatic moieties are linked via ester and possibly ether bonds., Conclusions: High similarity of aliphatic moieties in the cutan and the cuticular wax component indicated a common biosynthetic origin. In order to exclude species-specific peculiarities of A. americana and to place our results in a broader context, cuticular waxes, cutin and cutan of Clivia miniata, Ficus elastica and Prunus laurocerasus leaves were also investigated. A detailed comparison showed compositional and structural differences, indicated that cutan was only found in leaves of perennial evergreen A. americana and C. miniata, and made clear that the phenomenon of cutan is possibly less present in plant species than suggested in the literature., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The efficacy of the cuticular transpiration barrier and its resistance to elevated temperatures are significantly higher in a typical water-saver than in a water-spender plant growing in hot desert., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3 lo Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype. Overall, we found that the proportion of FOXP3 + IL-17 + cells in T1D subjects pre-diagnosis was unchanged compared with healthy controls. However, stratification by IL2RA single-nucleotide polymorphisms revealed that T1D subjects with the rs3118470 CC risk variant have Tregs with IL-2 signaling defects and an increased proportion of FOXP3 + IL-17 + cells before diagnosis. These data suggest a potential mechanism for genetically controlled loss of Treg function via dysfunctional IL-2 signaling in T1D.