International Immunology, Vol. 14, No. 2, 177-187,
February 2002
© 2002 Japanese Society for Immunology
BCR signal through 
4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation
Departments of Immunology and
1 Pharmacology I, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
2 Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
Correspondence to: N. Sakaguchi; E-mail: nobusaka{at}kaiju.medic.kumamoto-u.ac.jp
4 potentially mediates BCR signals through a rapamycin-sensitive TOR pathway. To investigate a potential role for 4 in B cell activation, the 4 gene was disrupted conditionally in B cells by mating male CD19-Cre mice with female 4-floxed mice. CD19-Cre+/4flox mice showed loss of 4 protein in B lineage cells and a decreased number of phenotypically normal mature B cells. Compared to normal B cells, 4- B cells showed a decreased proliferation in response to the B cell stimulants (anti-IgM antibody plus IL-4, anti-CD40 mAb and lipopolysaccharide), and a reduced S6 kinase activation and rapamycin sensitivity. While CD19-Cre+/4flox mice showed impaired antibody responses to both T cell-independent and T cell-dependent (TD) antigens, the TD antigen response was markedly impaired as demonstrated by reduced isotype switching, reduced germinal center formation and reduced V region somatic hypermutation. These results show that 4 plays a pivotal role in antigen-specific signal transduction during B cell activation and differentiation in vivo.
Keywords: class switch, gene knockout mouse, germinal center, S6 kinase, V region somatic hypermutation
Transmitting editor: T. Watanabe
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. D. Cygnar, X. Gao, D. Pan, and T. P. Neufeld The Phosphatase Subunit Tap42 Functions Independently of Target of Rapamycin to Regulate Cell Division and Survival in Drosophila Genetics, June 1, 2005; 170(2): 733 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kong, C. J. Fox, J. Mu, L. Solt, A. Xu, R. M. Cinalli, M. J. Birnbaum, T. Lindsten, and C. B. Thompson The PP2A-Associated Protein {alpha}4 Is an Essential Inhibitor of Apoptosis Science, October 22, 2004; 306(5696): 695 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dupont and A.N. Warrens The evolving role of sirolimus in renal transplantation QJM, June 1, 2003; 96(6): 401 - 409. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pasparakis, M. Schmidt-Supprian, and K. Rajewsky I{kappa}B Kinase Signaling Is Essential for Maintenance of Mature B Cells J. Exp. Med., September 16, 2002; 196(6): 743 - 752. [Abstract] [Full Text] [PDF]
|
|