Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b
Authors: S Mariathasan
H Nishina
T Sasaki
J M Penninger
J Le
P S Ohashi
K Bachmaier
D Bouchard
C Krawczyk
S Lipkowitz
I Kozieradzki
Y Y Kong
I Sarosi
A Oliveira-dos-Santos
A Wakeham
A Itie
Journal: Nature (2000)
Discipline: Multidisciplinary
Keywords: antigen receptors; co-stimulatory receptors; immunity; tolerance; autoimmunity
Affiliations: Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.

Abstract:  The signalling thresholds of antigen receptors and co-stimulatory receptors determine immunity or tolerance to self molecules. Changes in co-stimulatory pathways can lead to enhanced activation of lymphocytes and autoimmunity, or the induction of clonal anergy. The molecular mechanisms that maintain immunotolerance in vivo and integrate co-stimulatory signals with antigen receptor signals in T and B lymphocytes are poorly understood. Members of the Cbl/Sli family of molecular adaptors function downstream from growth factor and antigen receptors. Here we show that gene-targeted mice lacking the adaptor Cbl-b develop spontaneous autoimmunity characterized by auto-antibody production, infiltration of activated T and B lymphocytes into multiple organs, and parenchymal damage. Resting cbl-b(-/-) lymphocytes hyperproliferate upon antigen receptor stimulation, and cbl-b(-/-) T cells display specific hyperproduction of the T-cell growth factor interleukin-2, but not interferon-gamma or tumour necrosis factor-alpha. Mutation of Cbl-b uncouples T-cell proliferation, interleukin-2 production and phosphorylation of the GDP/GTP exchange factor Vav1 from the requirement for CD28 co-stimulation. Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity. 

Retracted: No

PubPeer comments:
  Coordination polymers (CPs) are crystalline materials which are well known over the past few decades due to their various applications in the area of gas storage separation, removal of hazardous molecules, catalysis and biomedicine.[1u20134] - [2]. Zhang, D.; Wang, M. M.; Jiang, N.; Liu, Y.; Yu, X. N.; Zhang, H. B. Electrochemical Corrosion Behavior of Ni-Doped ZnO Thin Film Coated on Low Carbon Steel Substrate in 3.5% NaCl Solution. Int. J. Electrochem. Sci. 2020, 15, 4117u20134126. - [3]. Su, J.; Sheng, Z.; Xie, L.; Li, G.; Liu, A. X. Fast Splitting Based Tag Identification Algorithm for anti-Collision in UHF RFID System. IEEE Trans. Commun. 2019, 67, 2527u20132538. DOI: 10.1109 TCOMM.2018.2884001. - [4]. Arshad, M.; Du, H. L.; Javed, M. S.; Maqsood, A.; Ashraf, I.; Hussain, S.; Ma, W. L.; Ran, H. P. Fabrication, Structure, and Frequency-Dependent Electrical and Dielectric Properties of Sr-Doped BaTiO3 Ceramics. Ceram. Int. 2020, 46, 2238u20132246. DOI:10.1016 j.ceramint.2019.09.208  Coordination polymer is apparently a broad enough term to cover inorganic ceramics, anti-corrosion coatings, and RFID algorithms. This particular cluster of nonsensical references is used in scores of papers, presumably [from the same production line] , as if the authors were signing their work.  Infrared spectra (IR) (KBr pellets) were recorded on a Nexus 870 FTIR spectrometer in the range of 400u20134000 cm-1. No FTIR results are mentioned. -------------------------------- The CCDC database informs me that the crystal-structure determination data and parameters for the present compounds were both deposited there as data sets [2015759] and [2015760] , with Haitao Yuan of Bohai University as the crystallographer. No-one of that name is credited in the paper. By my count, Haitao Yuan provided the CCDC database [with 134 data sets] , many of them used in problematic papers. ,