Abstract:
:Act1 is a negative regulator of B-cell activation factor of the TNF family (BAFF) and CD40L-induced signaling. BALB/C mice lacking Act1 develop systemic autoimmunity resembling systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). SLE and SjS are characterized by anti-nuclear IgG autoantibody (ANA-IgG) production and inflammation of peripheral tissues. As autoantibody production can occur in a T-cell dependent or T-cell independent manner, we investigated the role of T-cell help during Act1-mediated autoimmunity. Act1-deficiency was bred onto C57Bl/6 (B6.Act1(-/-) ) mice and B6.TCRβ(-/-) TCRδ(-/-) Act1(-/-) (TKO) mice were generated. While TCRβ/δ-sufficient B6.Act1(-/-) mice developed splenomegaly and lymphadenopathy, hypergammaglobulinemia, elevated levels of ANA-IgG, and kidney pathology, TKO mice failed to develop any such signs of disease. Neither B6.Act1(-/-) nor TKO mice developed SjS-like disease, suggesting that epigenetic interactions on the BALB/C background are responsible for this phenotype in BALB/C.Act1(-/-) mice. Interestingly, BAFF-driven transitional B-cell abnormalities, previously reported in BALB/C.Act1(-/-) mice, were intact in B6.Act1(-/-) mice and largely independent of T cells. In conclusion, T cells are necessary for the development of SLE-like disease in B6.Act1(-/-) mice, but not BAFF-driven transitional B-cell differentiation.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Johnson AC,Davison LM,Giltiay NV,Vareechon C,Li X,Jørgensen TNdoi
10.1002/eji.201142238subject
Has Abstractpub_date
2012-07-01 00:00:00pages
1695-705issue
7eissn
0014-2980issn
1521-4141journal_volume
42pub_type
杂志文章abstract::The interaction between TCR and peptide-MHC is well described in terms of the recognition of the peptide, but the recognition of the MHC is less well understood. At issue is whether particular V gene products may have higher affinity for some MHC over others and to what extent the bound peptide influences V gene selec...
journal_title:European journal of immunology
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abstract::We identified the presence in the Aleutian skate, Bathyraja aleutica, of two classes of immunoglobulins (Ig), a high molecular weight Ig analogous to mammalian IgM and a low molecular weight Ig, similarly to the spiny rasp skate, Raja kenojei, (Kobayashi, K. et al., Mol. Immunol. 1984. 21: 397), using an immunological...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830190409
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:1993-01-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830231017
更新日期:1993-10-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200201)32:1<18::AID-IMMU18>3.0.C
更新日期:2002-01-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:2004-05-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270209
更新日期:1997-02-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200731
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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