title: The MHC class II cofactor HLA-DM interacts with Ig in B cells.
abstract: B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Henriette
authors.initials: H
authors.lastname: Macmillan
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strohman
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sashi
authors.initials: S
authors.lastname: Ayyangar
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Narendiran
authors.initials: N
authors.lastname: Rajasekaran
authors.affiliation: Life Technologies, South San Francisco, CA 94080, USA.
authors.forename: Armin
authors.initials: A
authors.lastname: Spura
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Hessell
authors.affiliation: Faculté de médecine Lyon-Sud, BP12 69921 Oullins cedex, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Madec
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002451:Cell Compartmentation / Q000276:immunology; D045744:Cell Line, Tumor; D011992:Endosomes / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D007140:Immunoglobulin Fab Fragments; D011947:Receptors, Antigen, B-Cell
references.citation: Blood. 1987 May;69(5):1307-14
references.pmid: 3567358
references.citation: J Immunol. 1990 Jun 1;144(11):4101-9
references.pmid: 2187925
references.citation: PLoS Genet. 2008 Apr 25;4(4):e1000024
references.pmid: 18437207
references.citation: Annu Rev Immunol. 2012;30:429-57
references.pmid: 22224772
references.citation: J Immunol. 2006 Oct 15;177(8):5430-9
references.pmid: 17015729
references.citation: J Virol. 2001 Sep;75(17):8340-7
references.pmid: 11483779
references.citation: Immunol Lett. 2010 Nov 30;134(1):75-82
references.pmid: 20837062
references.citation: J Exp Med. 1995 Jun 1;181(6):1957-63
references.pmid: 7539034
references.citation: J Immunol. 1996 May 1;156(9):3541-9
references.pmid: 8617984
references.citation: Nat Immunol. 2011 Jan;12(1):54-61
references.pmid: 21131964
references.citation: Blood. 1984 Jan;63(1):140-6
references.pmid: 6418229
references.citation: Nat Rev Immunol. 2010 Jun;10(6):403-14
references.pmid: 20498667
references.citation: J Immunol. 2001 Dec 15;167(12):6849-58
references.pmid: 11739502
references.citation: Immunity. 2005 Feb;22(2):221-33
references.pmid: 15723810
references.citation: Curr Opin Immunol. 1998 Feb;10(1):67-73
references.pmid: 9523114
references.citation: Nat Methods. 2006 Dec;3(12):995-1000
references.pmid: 17072308
references.citation: Nat Rev Immunol. 2003 Aug;3(8):621-9
references.pmid: 12974477
references.citation: Trends Immunol. 2008 Mar;29(3):141-7
references.pmid: 18261958
references.citation: J Exp Med. 1985 Oct 1;162(4):1193-207
references.pmid: 2413154
references.citation: Annu Rev Immunol. 2009;27:591-619
references.pmid: 19132916
references.citation: Immunol Cell Biol. 2011 Mar;89(3):388-95
references.pmid: 21301478
references.citation: J Exp Med. 2002 Apr 15;195(8):1053-62
references.pmid: 11956296
references.citation: Immunology. 2010 Sep;131(1):18-32
references.pmid: 20408893
references.citation: J Immunol. 2003 Sep 1;171(5):2331-7
references.pmid: 12928379
references.citation: Cell. 1978 May;14(1):9-20
references.pmid: 667938
references.citation: J Immunol. 1999 Jun 15;162(12):7171-80
references.pmid: 10358163
references.citation: J Virol. 2004 Dec;78(23):13232-52
references.pmid: 15542675
references.citation: Curr Opin Immunol. 2007 Feb;19(1):93-8
references.pmid: 17140785
references.citation: PLoS One. 2013 Jul 25;8(7):e69228
references.pmid: 23976922
references.citation: EMBO J. 2007 Apr 18;26(8):2137-47
references.pmid: 17396153
references.citation: Biomed Pharmacother. 1997;51(10):480-7
references.pmid: 9863510
references.citation: Annu Rev Immunol. 1990;8:773-93
references.pmid: 2188679
references.citation: Nat Biotechnol. 2002 May;20(5):473-7
references.pmid: 11981560
references.citation: J Immunol. 2003 Sep 1;171(5):2374-83
references.pmid: 12928384
references.citation: J Biol Chem. 1998 Oct 16;273(42):27557-64
references.pmid: 9765288
references.citation: Immunity. 1998 Sep;9(3):377-83
references.pmid: 9768757
references.citation: Nat Rev Immunol. 2008 Jan;8(1):22-33
references.pmid: 18097447
references.citation: Immunity. 2003 Aug;19(2):183-92
references.pmid: 12932352
references.citation: Cell. 2012 Dec 21;151(7):1557-68
references.pmid: 23260142
references.citation: J Immunol. 1981 Sep;127(3):881-8
references.pmid: 6790620
references.citation: Nat Immunol. 2007 Oct;8(10):1041-8
references.pmid: 17878914
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11276-81
references.pmid: 22733780
references.citation: Science. 1986 May 23;232(4753):1001-4
references.pmid: 2422757
references.citation: Nat Struct Mol Biol. 2013 Jan;20(1):90-8
references.pmid: 23222639
references.citation: Anal Biochem. 2008 Jun 15;377(2):209-17
references.pmid: 18405656
references.citation: J Immunol. 1988 Feb 15;140(4):1063-8
references.pmid: 2449493
references.citation: Biochim Biophys Acta. 2012 Jan;1824(1):14-21
references.pmid: 21782984
references.citation: Lab Invest. 2006 Aug;86(8):853-64
references.pmid: 16783395
references.citation: Biochim Biophys Acta. 1995 Feb 23;1243(2):287-9
references.pmid: 7873576
references.citation: Nature. 1985 Apr 11-17;314(6011):537-9
references.pmid: 3157869
references.citation: J Immunol. 1980 Jul;125(1):293-9
references.pmid: 6966655
references.citation: Immunol Rev. 2005 Oct;207:242-60
references.pmid: 16181341
references.citation: Genome Biol. 2006;7(10):R100
references.pmid: 17076895
references.citation: Mol Immunol. 2011 Jun;48(11):1281-6
references.pmid: 21144589
references.citation: Nat Immunol. 2004 Jul;5(7):685-92
references.pmid: 15224094