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A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation

Chu, Yuanyuan; Soberon, Valeria; Glockner, Laura; Beyaert, Rudi; Massoumi, Ramin LU ; van Loo, Geert; Krappmann, Daniel and Schmidt-Supprian, Marc (2012) In Journal of Immunology 189(9). p.4437-4443
Abstract
The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negative regulators of NF-kappa B signaling. Both can act by removing nonproteolytic K63-linked polyubiquitin chains from an overlapping set of signaling molecules. In B cells, A20 deficiency results in hyperactivity, loss of immune homeostasis, inflammation, and autoimmunity. The reported consequences of CYLD deficiency are controversial, ranging from an absence of effects to dramatic B cell hyperplasia. These differences could be due to varying compensation for the loss of CYLD function by A20. Therefore, to explore potential overlapping physiological functions between A20 and CYLD, we generated and characterized A20/CYLD double-deficient B cells.... (More)
The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negative regulators of NF-kappa B signaling. Both can act by removing nonproteolytic K63-linked polyubiquitin chains from an overlapping set of signaling molecules. In B cells, A20 deficiency results in hyperactivity, loss of immune homeostasis, inflammation, and autoimmunity. The reported consequences of CYLD deficiency are controversial, ranging from an absence of effects to dramatic B cell hyperplasia. These differences could be due to varying compensation for the loss of CYLD function by A20. Therefore, to explore potential overlapping physiological functions between A20 and CYLD, we generated and characterized A20/CYLD double-deficient B cells. Interestingly, the lack of both A20 and CYLD did not exacerbate the developmental defects and hyperresponsive activity of A20-deficient B cells. In addition, the extent of B cell activation after in vitro stimulation with anti-CD40, LPS, and CpG was comparable in B cells lacking A20/CYLD and A20 alone. However, in response to BCR cross-linking, we observed small but reproducible additive effects of the lack of A20 and CYLD. Taken together, our results demonstrate that A20 and CYLD do not share significant functions during B cell development and activation. The Journal of Immunology, 2012, 189: 4437-4443. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
189
issue
9
pages
4437 - 4443
publisher
American Association of Immunologists
external identifiers
  • wos:000310200600030
  • scopus:84867918803
ISSN
1550-6606
DOI
10.4049/jimmunol.1200396
language
English
LU publication?
yes
id
2bff1c0e-ffc5-42a2-9008-b51849a6ca7d (old id 3283592)
date added to LUP
2013-01-07 09:41:31
date last changed
2017-07-09 04:10:38
@article{2bff1c0e-ffc5-42a2-9008-b51849a6ca7d,
  abstract     = {The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negative regulators of NF-kappa B signaling. Both can act by removing nonproteolytic K63-linked polyubiquitin chains from an overlapping set of signaling molecules. In B cells, A20 deficiency results in hyperactivity, loss of immune homeostasis, inflammation, and autoimmunity. The reported consequences of CYLD deficiency are controversial, ranging from an absence of effects to dramatic B cell hyperplasia. These differences could be due to varying compensation for the loss of CYLD function by A20. Therefore, to explore potential overlapping physiological functions between A20 and CYLD, we generated and characterized A20/CYLD double-deficient B cells. Interestingly, the lack of both A20 and CYLD did not exacerbate the developmental defects and hyperresponsive activity of A20-deficient B cells. In addition, the extent of B cell activation after in vitro stimulation with anti-CD40, LPS, and CpG was comparable in B cells lacking A20/CYLD and A20 alone. However, in response to BCR cross-linking, we observed small but reproducible additive effects of the lack of A20 and CYLD. Taken together, our results demonstrate that A20 and CYLD do not share significant functions during B cell development and activation. The Journal of Immunology, 2012, 189: 4437-4443.},
  author       = {Chu, Yuanyuan and Soberon, Valeria and Glockner, Laura and Beyaert, Rudi and Massoumi, Ramin and van Loo, Geert and Krappmann, Daniel and Schmidt-Supprian, Marc},
  issn         = {1550-6606},
  language     = {eng},
  number       = {9},
  pages        = {4437--4443},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation},
  url          = {http://dx.doi.org/10.4049/jimmunol.1200396},
  volume       = {189},
  year         = {2012},
}