title: Arginine methylation regulates antibody responses through modulating cell division and isotype switching in B cells.
abstract: Protein arginine methylation plays crucial roles, including signal transduction, transcriptional control, cell proliferation and/or differentiation. B cells undergo clonal division, isotype switching and differentiate into antibody forming cells following stimulation with Toll-like receptor-ligand, lipopolysaccharide (LPS) and T cell-derived signals, including CD40-ligand (CD40-L) and interleukin 4 (IL-4). Whether protein arginine methylation affects B cell division and/or isotype switching to IgG1 in response to LPS, IL-4, and CD40-L was examined using the arginine methyl transferase inhibitor adenosine-2',3'-dialdehyde (AdOx). Addition of AdOx substantially reduced the number of division cycles of stimulated B cells, whereas cell viability remained intact. Upon stimulation with LPS/IL-4/CD40-L, the proportion of surface IgG1 positive cells in each division cycle was slightly diminished by AdOx. However, the degree of expression of γ1 germ line transcript and activation-induced cytidine deaminase (AID) in response to LPS/IL-4/CD40-L were unaffected by addition of AdOx, suggesting that AdOx influences class switch recombination independent of AID expression through transcriptional control. Taken together, arginine methylation appears to be involved in B cell isotype switching, as well as in clonal expansion of B cells in response to LPS/IL-4/CD40-L.
authors.affiliation: Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
authors.forename: Kikumi
authors.initials: K
authors.lastname: Hata
authors.forename: Junichiro
authors.initials: J
authors.lastname: Mizuguchi
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002455:Cell Division; D049109:Cell Proliferation; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational
chemical_list: D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D023201:CD40 Ligand; D015847:Interleukin-4; D001120:Arginine