Journal
MOLECULAR IMMUNOLOGY
Volume 46, Issue 6, Pages 1031-1041Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2008.08.272
Keywords
IgE; GC B-cells; Arginine methylation; IL-4; JAK-STAT; Allergy
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency
- JSPS KAKENHI [17590440]
- Grants-in-Aid for Scientific Research [17590440] Funding Source: KAKEN
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Antigen (Ag)-driven B cells undergo antibody (Ab) affinity maturation and class switching in germinal center (GC) B cells. GANP is one of the molecules required for Ab affinity maturation. We herein found an increase of IgE in B cell ganp-deficient mice and studied the signal transduction pathway regulated by GANP. GANP suppresses the STAT-mediated transcription activity in GC B cells with the regulation of arginine methyltransferase activity by the interaction with JAK-binding protein arginine methyltransferase (PRMT) 5 and JAK1/JAK3 that are responsible for STAT6 activation. The prmt5 mRNA was up-regulated in B cells after stimulation in vitro and in vivo in GC B cells. The loss of GANP caused up-regulation of phosphorylation and arginine dimethylation of STAT6 in B cells after stimulation with LIPS and IL-4 in vitro. On the contrary, GANP over-expressed B cells in ganp gene-transgenic mice showed a low STAT6 phosphorylation after stimulation. The over-expression of PRMT5 caused the up-regulation of STAT6-mediated gene transcription, which was also suppressed by the co-transfection of GANP, in luciferase reporter assay. GANP down-regulates JAK1/JAK3 to STAT6-signaling with regulation of arginine methylation activity, which might be responsible for the B cell endogenous suppressive mechanism of hyper-IgE. (C) 2008 Elsevier Ltd. All rights reserved.
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