title: Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.
abstract: Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.
authors: Department of Human Anatomy (JZ).
authors: Jie
authors: J
authors: Zhang
authors: Na
authors: N
authors: Niu
authors: Bingjie
authors: B
authors: Li
authors: Michael A
authors: MA
authors: McNutt
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007074:Immunoglobulin G; D012333:RNA, Messenger; D003165:Complement System Proteins
keywords: CD64; active immunity; complement; endogenous IgG; neuron
references: Dev Cell. 2003 Jun;4(6):841-52
references: 12791269
references: Cell Mol Life Sci. 2011 Jul;68(14):2481-92
references: 21061041
references: J Comp Neurol. 1997 Jul 28;384(2):271-82
references: 9215722
references: Haematologica. 2010 Jan;95(1):71-8
references: 19648166
references: FASEB J. 2004 Jan;18(1):182-4
references: 14630707
references: J Neurosci Res. 2008 Dec;86(16):3556-65
references: 18756515
references: J Neurosci. 2002 Feb 1;22(3):782-90
references: 11826108
references: Cancer Res. 2003 Oct 1;63(19):6488-95
references: 14559841
references: J Neurol. 2007 May;254 Suppl 2:II2-7
references: 17503123
references: J Clin Pathol. 1983 Mar;36(3):312-5
references: 6826780
references: Neuromolecular Med. 2010 Jun;12(2):179-92
references: 19763906
references: Neurology. 1988 Nov;38(11):1775-80
references: 3185914
references: Neuroscience. 2009 Feb 6;158(3):1122-32
references: 18848864
references: J Neurosci. 2008 Nov 19;28(47):12199-211
references: 19020014
references: Nat Med. 2003 Apr;9(4):431-8
references: 12612546
references: Int J Biochem Cell Biol. 2008;40(8):1604-15
references: 18243769
references: Cancer Immunol Immunother. 2012 Jan;61(1):89-99
references: 21850469
references: Haematologica. 2009 Sep;94(9):1316-20
references: 19734426
references: Int J Biochem Cell Biol. 2011 Apr;43(4):556-63
references: 21167303
references: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14104-9
references: 17715065
references: Curr Pharm Des. 2012;18(2):200-8
references: 22229581
references: Neurochem Int. 2007 Jan;50(1):39-50
references: 16971022
references: Cancer Res. 2003 Aug 15;63(16):5073-83
references: 12941837
references: Front Biosci (Landmark Ed). 2011 Jun 01;16:2921-60
references: 21622213
references: Lab Invest. 2009 Jun;89(6):636-44
references: 19333236
references: Immunol Rev. 2006 Oct;213:48-65
references: 16972896
references: Mult Scler. 1998 Jun;4(3):111-7
references: 9762657
references: J Neurosci. 2005 Mar 9;25(10):2566-75
references: 15758166
references: J Neurochem. 1999 Feb;72(2):565-75
references: 9930728
references: J Immunol. 2001 Jun 1;166(11):6861-8
references: 11359846
references: J Neurosci Res. 2002 Jul 1;69(1):110-6
references: 12111822
references: Clin Chem. 1980 Jan;26(1):115-6
references: 7356542
references: Glia. 2001 Nov;36(2):165-79
references: 11596125