Double knockout mice show BASH and PKCdelta have different epistatic relationships in B cell maturation and CD40-mediated activation.
Immunol Lett
; 105(1): 48-54, 2006 May 15.
Article
in En
| MEDLINE
| ID: mdl-16481047
ABSTRACT
The development and survival of mature B cells requires an antigen-independent signal from the B cell receptor (BCR) through an adaptor protein containing an SH2 domain, BASH (BLNK/SLP-65). It also requires signaling through BAFF and the BAFF receptor (BAFF-R), and is negatively regulated by protein kinase Cdelta (PKCdelta). In PKCdelta-deficient mice, B cell maturation occurs independently of the BAFF receptor (BAFF-R), indicating that BAFF-R signaling promotes maturation by inhibiting the negative function of PKCdelta. To clarify which of the two signaling pathways plays the primary role in B cell maturation, we crossed BASH-deficient mice with PKCdelta-deficient mice to generate BASH/PKCdelta-double knockout (DKO) mice. In the DKO mice, B cell maturation was blocked at the transitional type 1 (T1) stage and B cells were prone to apoptosis, in common with BASH-deficient mice. This indicates that BASH-mediated BCR signaling primarily controls B cell survival and maturation, with BAFF-R signaling and its inhibition of PKCdelta acting as a secondary regulator. By contrast, CD40-mediated proliferation and antibody production, which are low in BASH-deficient mice, were rescued in the DKO mice, indicating that the suppression of CD40-mediated B cell activation by PKCdelta is epistatic to BASH-mediated promotion. The physiological relevance of these opposing hierarchical effects of BASH and PKCdelta in the regulation of B cell maturation and activation is discussed.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
B-Lymphocytes
/
Protein Kinase C-delta
Limits:
Animals
Language:
En
Journal:
Immunol Lett
Year:
2006
Document type:
Article
Affiliation country:
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS