66 research outputs found

    Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

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    Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies

    The Spin Structure Function g1pg_1^{\rm p} of the Proton and a Test of the Bjorken Sum Rule

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    New results for the double spin asymmetry A1pA_1^{\rm p} and the proton longitudinal spin structure function g1pg_1^{\rm p} are presented. They were obtained by the COMPASS collaboration using polarised 200 GeV muons scattered off a longitudinally polarised NH3_3 target. The data were collected in 2011 and complement those recorded in 2007 at 160\,GeV, in particular at lower values of xx. They improve the statistical precision of g1p(x)g_1^{\rm p}(x) by about a factor of two in the region x0.02x\lesssim 0.02. A next-to-leading order QCD fit to the g1g_1 world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, ΔΣ\Delta \Sigma ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of g1pg_1^{\rm p}. The uncertainty of ΔΣ\Delta \Sigma is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function g1NS(x,Q2)g_1^{\rm NS}(x,Q^2) yields as ratio of the axial and vector coupling constants gA/gV=1.22±0.05 (stat.)±0.10 (syst.)|g_{\rm A}/g_{\rm V}| = 1.22 \pm 0.05~({\rm stat.}) \pm 0.10~({\rm syst.}), which validates the sum rule to an accuracy of about 9\%.Comment: 19 pages, 8 figures and table

    Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

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    A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality Q2>1Q^{2}>1 (GeV/cc)2^2, invariant mass of the hadronic system W>5W > 5 GeV/c2c^2, Bjorken scaling variable in the range 0.003<x<0.40.003 < x < 0.4, fraction of the virtual photon energy carried by the hadron in the range 0.2<z<0.80.2 < z < 0.8, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/c)2<PhT2<3c)^2 < P_{\rm{hT}}^{2} < 3 (GeV/cc)2^2. The multiplicities are presented as a function of PhT2P_{\rm{hT}}^{2} in three-dimensional bins of xx, Q2Q^2, zz and compared to previous semi-inclusive measurements. We explore the small-PhT2P_{\rm{hT}}^{2} region, i.e. PhT2<1P_{\rm{hT}}^{2} < 1 (GeV/cc)2^2, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger PhT2P_{\rm{hT}}^{2}, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small PhT2P_{\rm{hT}}^{2} to study the dependence of the average transverse momentum PhT2\langle P_{\rm{hT}}^{2}\rangle on xx, Q2Q^2 and zz. The power-law behaviour of the multiplicities at large PhT2P_{\rm{hT}}^{2} is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

    Spin alignment and violation of the OZI rule in exclusive ω\omega and ϕ\phi production in pp collisions

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    Exclusive production of the isoscalar vector mesons ω\omega and ϕ\phi is measured with a 190 GeV/c/c proton beam impinging on a liquid hydrogen target. Cross section ratios are determined in three intervals of the Feynman variable xFx_{F} of the fast proton. A significant violation of the OZI rule is found, confirming earlier findings. Its kinematic dependence on xFx_{F} and on the invariant mass MpVM_{p\mathrm{V}} of the system formed by fast proton pfastp_\mathrm{fast} and vector meson VV is discussed in terms of diffractive production of pfastVp_\mathrm{fast}V resonances in competition with central production. The measurement of the spin density matrix element ρ00\rho_{00} of the vector mesons in different selected reference frames provides another handle to distinguish the contributions of these two major reaction types. Again, dependences of the alignment on xFx_{F} and on MpVM_{p\mathrm{V}} are found. Most of the observations can be traced back to the existence of several excited baryon states contributing to ω\omega production which are absent in the case of the ϕ\phi meson. Removing the low-mass MpVM_{p\mathrm{V}} resonant region, the OZI rule is found to be violated by a factor of eight, independently of xFx_\mathrm{F}.Comment: 23 pages, 13 figures and 5 table

    Collins and Sivers asymmetries in muonproduction of pions and kaons off transversely polarised proton

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    Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise.Comment: 15 pages, 13 figures and 1 tabl
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