title: Uncoupling CD21 and CD19 of the B-cell coreceptor.
abstract: Complement receptors (CRs) CD21 and CD35 form a coreceptor with CD19 and CD81 on murine B cells that when coligated with the B-cell receptor lowers the threshold of activation by several orders of magnitude. This intrinsic signaling role is thought to explain the impaired humoral immunity of mice bearing deficiency in CRs. However, CRs have additional roles on B cells independent of CD19, such as transport of C3-coated immune complexes and regulation of C4 and C3 convertase. To test whether association of CR with CD19 is necessary for their intrinsic activation-enhancing role, knockin mice expressing mutant receptors, Cr2(Delta/Deltagfp), that bind C3 ligands but do not signal through CD19 were constructed. We found that uncoupling of CR and CD19 significantly diminishes survival of germinal center B cells and secondary antibody titers. However, B memory is less impaired relative to mice bearing a complete deficiency in CRs on B cells. These findings confirm the importance of interaction of CR and CD19 for coreceptor activity in humoral immunity but identify a role for CR in B-cell memory independent of CD19.
authors.affiliation: The Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Barrington
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schneider
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Pitcher
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Mempel
authors.forename: Minghe
authors.initials: M
authors.lastname: Ma
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Barteneva
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D017463:Receptors, Complement 3b / Q000235:genetics / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D018941:Antigens, CD19; D006241:Haptens; D018398:Homeodomain Proteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; C064658:RAG-1 protein; D049452:Green Fluorescent Proteins; D006433:Hemocyanins
references.citation: Nature. 1988 Aug 25;334(6184):676-82
references.pmid: 3261841
references.citation: J Immunol. 1998 Jun 1;160(11):5273-9
references.pmid: 9605124
references.citation: Nature. 1995 Jul 27;376(6538):352-5
references.pmid: 7543183
references.citation: J Exp Med. 1996 Apr 1;183(4):1857-64
references.pmid: 8666942
references.citation: J Exp Med. 2003 Aug 18;198(4):591-602
references.pmid: 12925675
references.citation: J Immunol. 1998 May 15;160(10):4776-87
references.pmid: 9590224
references.citation: Immunol Today. 1994 Sep;15(9):437-42
references.pmid: 7524521
references.citation: J Exp Med. 1993 Oct 1;178(4):1407-17
references.pmid: 7690834
references.citation: J Exp Med. 1999 Aug 2;190(3):399-410
references.pmid: 10430628
references.citation: J Immunol. 2001 Sep 15;167(6):3190-200
references.pmid: 11544305
references.citation: Nat Immunol. 2008 Jan;9(1):54-62
references.pmid: 18037889
references.citation: J Exp Med. 2000 Feb 7;191(3):475-84
references.pmid: 10662793
references.citation: Adv Immunol. 1996;61:201-83
references.pmid: 8834497
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10844-9
references.pmid: 9380722
references.citation: Int Immunol. 2004 Oct;16(10):1411-22
references.pmid: 15326094
references.citation: J Immunol. 1994 Mar 15;152(6):2899-903
references.pmid: 8144890
references.citation: J Immunol. 2005 Mar 15;174(6):3264-72
references.pmid: 15749857
references.citation: J Immunol. 1999 Apr 15;162(8):4377-80
references.pmid: 10201971
references.citation: Annu Rev Immunol. 1994;12:991-1045
references.pmid: 8011301
references.citation: Biochim Biophys Acta. 2003 Sep 23;1651(1-2):1-4
references.pmid: 14499583
references.citation: Science. 2000 Jan 21;287(5452):498-501
references.pmid: 10642554
references.citation: J Exp Med. 1990 Aug 1;172(2):665-8
references.pmid: 1695671
references.citation: J Exp Med. 1999 Oct 18;190(8):1165-74
references.pmid: 10523614
references.citation: Vaccine. 2008 Dec 30;26 Suppl 8:I86-93
references.pmid: 19388171
references.citation: Immunity. 1996 Mar;4(3):251-62
references.pmid: 8624815
references.citation: J Immunol. 2008 Sep 1;181(5):2953-9
references.pmid: 18713965
references.citation: J Exp Med. 2002 Nov 4;196(9):1189-99
references.pmid: 12417629
references.citation: Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3357-61
references.pmid: 8622941
references.citation: J Immunol. 2004 Jan 1;172(1):370-80
references.pmid: 14688345
references.citation: J Immunol Methods. 2001 Dec 1;258(1-2):97-109
references.pmid: 11684127
references.citation: Science. 1996 Jan 19;271(5247):348-50
references.pmid: 8553069
references.citation: Immunity. 2009 Feb 20;30(2):264-76
references.pmid: 19185517
references.citation: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12708-12
references.pmid: 10535987
references.citation: Nat Immunol. 2007 Sep;8(9):992-1000
references.pmid: 17660822
references.citation: Science. 1991 Oct 4;254(5028):102-5
references.pmid: 1718035
references.citation: Immunity. 2001 Feb;14(2):169-79
references.pmid: 11239449
references.citation: Am J Pathol. 2007 Apr;170(4):1258-66
references.pmid: 17392165
references.citation: Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1-13
references.pmid: 2700931
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13158-62
references.pmid: 9371816
references.citation: Science. 1998 Apr 24;280(5363):582-5
references.pmid: 9554848
references.citation: Eur J Immunol. 2006 Sep;36(9):2384-93
references.pmid: 16906534
references.citation: J Immunol. 2001 Jul 1;167(1):163-72
references.pmid: 11418645
references.citation: Eur J Immunol. 1993 Apr;23(4):969-72
references.pmid: 8458382
references.citation: Immunity. 2002 Dec;17(6):713-23
references.pmid: 12479818
references.citation: J Exp Med. 2005 Mar 21;201(6):993-1005
references.pmid: 15767369
references.citation: Am J Pathol. 2002 Sep;161(3):1077-86
references.pmid: 12213736
references.citation: J Exp Med. 1997 Apr 21;185(8):1505-10
references.pmid: 9126932
references.citation: Immunity. 2005 Jun;22(6):749-61
references.pmid: 15963789
references.citation: Eur J Immunol. 1991 Oct;21(10):2501-6
references.pmid: 1717285
references.citation: J Immunol. 1991 Jul 1;147(1):224-30
references.pmid: 1828822
references.citation: J Immunol. 2005 Sep 1;175(5):2859-67
references.pmid: 16116172
references.citation: Microbes Infect. 2003 Mar;5(3):205-12
references.pmid: 12681409
references.citation: Nat Immunol. 2000 Jul;1(1):31-6
references.pmid: 10881171
references.citation: Crit Rev Immunol. 2004;24(1):39-65
references.pmid: 14995913
references.citation: J Immunol. 1990 May 1;144(9):3581-91
references.pmid: 2139460
references.citation: Annu Rev Immunol. 1994;12:117-39
references.pmid: 8011279