TRAF2 Differentially Regulates the Canonical and Noncanonical Pathways of NF-κB Activation in Mature B Cells
To examine the role of the TNF-R superfamily signaling protein TRAF2 in mature B cell development and NF-κB activation, conditionally TRAF2-deficient mice were produced. B cells lacking TRAF2 expression in these mice possessed a selective survival advantage, accumulated in the lymph nodes and spleni...
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Published in | Immunity (Cambridge, Mass.) Vol. 21; no. 5; pp. 629 - 642 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.11.2004
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Online Access | Get full text |
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Summary: | To examine the role of the TNF-R superfamily signaling protein TRAF2 in mature B cell development and NF-κB activation, conditionally TRAF2-deficient mice were produced. B cells lacking TRAF2 expression in these mice possessed a selective survival advantage, accumulated in the lymph nodes and splenic marginal zone, were larger in size, and expressed increased levels of CD21/35. These TRAF2-deficient B cells could not proliferate or activate the canonical NF-κB pathway in response to CD40 ligation. By contrast, noncanonical NF-κB activation was constitutively hyperactive, with TRAF2-deficient B cells exhibiting close to maximal processing of NF-κB2 from p100 to p52 and high levels of constitutive p52 and RelB DNA binding activity. These findings establish TRAF2 as a multifunctional regulator of NF-κB activation that mediates activation of the canonical pathway but acts as a negative regulator of the noncanonical pathway. This dual functionality explains the contrasting roles of TRAF2 in B cell maturation and activation. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2004.09.011 |