NF-kappa B is required for CD38-mediated induction of C(gamma)1 germline transcripts in murine B lymphocytes
- Author(s)
- Kaku, H; Horikawa, K; Obata, Y; Kato, I; Okamoto, H; Sakaguchi, N; Gerondakis, S; Takatsu, K;
- Details
- Publication Year 2002-09,Volume 14,Issue #9,Page 1055-1064
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Ligation of CD38 on murine B cells with agonistic anti-CD38 mAb induces B cell proliferation, expression of germline gamma1 transcripts and enhances IL-5 receptor expression. This leads to Ig class switch recombination from the mu to gamma1 heavy chain gene, and high levels of IgM and lgG1 production, particularly in response to anti-CD38 and IL-5 co-stimulation. Although some of the post-receptor signaling events initiated by CD38 ligation have been characterized, signaling pathways involved in CD38-mediated germline gamma1 transcript expression in B cells are poorly understood. Here we show that CD38 ligation of murine splenic B cells activates members of the NF-kappaB/Rel family of proteins including c-Rel, p65 and p50. The activation patterns and kinetics of NF-kappaB-like proteins in CD38-stimulated B cells differ somewhat from those seen in CD40-stimulated B cells. Activation of NF-kappaB-like proteins by CD38 ligation is not observed in splenic B cells from Bruton's tyrosine kinase (Btk)-deficient (Btk(-/-)) mice, with inhibitors of protein kinase C (PKC) and phosphatidylinositol (PI)-3 kinase also suppressing NF-kappaB activation in CD38-activated B cells. We infer from these results that activation of Btk, PI-3 kinase and PKC play, at least in part, important roles in the induction of NF-kappaB in CD38-stimulated murine B cells. Consistent with a role for NF-kappaB/Rel signaling in CD38-mediated germline gamma1 transcript expression, p50(-/-) B cells show significant impairment of germline gamma1 transcript expression in response to CD38 ligation, whereas the CD40-induced response was not altered. In contrast, c-Rel(-/-) B cells show a severe impairment of germline gamma1 transcript expression in response to CD38 or CD40 ligation. These results indicate an essential role for NF-kappaB proteins in the induction of germline gamma1 transcripts by CD38-ligated murine B cells giving rise to IL-5-induced IgG1 production.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- CYCLIC ADP-RIBOSE; BRUTONS TYROSINE KINASE; CELL ANTIGEN RECEPTOR; DNA-BINDING SUBUNIT; C-CBL PROTOONCOGENE; SIGNAL-TRANSDUCTION; IL-5 RECEPTOR; CD38 LIGATION; ALPHA-CHAIN; PHOSPHATIDYLINOSITOL 3-KINASE
- Publisher's Version
- https://doi.org/10.1093/intimm/dxf072
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-09-01 12:00:00