title: High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations.
abstract: B-cell receptor (BCR) diversity is achieved centrally by rearrangement of Variable, Diversity, and Joining genes, and peripherally by somatic hypermutation and class-switching of the rearranged genes. Peripheral B-cell populations are subject to both negative and positive selection events in the course of their development that have the potential to shape the BCR repertoire. The origin of IgM(+)IgD(+)CD27(+) (IgM memory) cells is controversial. It has been suggested that they may be a prediversified, antigen-independent, population of cells or that they are a population of cells that develop in response to T-independent antigens. Most recently, it was suggested that the majority of IgM memory cells are directly related to switched memory cells and are early emigrants from the germinal center reaction. Advances in sequencing technology have enabled us to undertake large scale IGH repertoire analysis of transitional, naive, IgM memory and switched memory B-cell populations. We find that the memory B-cell repertoires differ from the transitional and naive repertoires, and that the IgM memory repertoire is distinct from that of class-switched memory. Thus we conclude that a large proportion of IgM memory cells develop in response to different stimuli than for class-switched memory cell development.
authors.affiliation: Department of Immunobiology, King's College London School of Medicine, London, UK.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Kipling
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Leong
authors.forename: Victoria
authors.initials: V
authors.lastname: Martin
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ademokun
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Dunn-Walters
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015321:Gene Rearrangement; D006801:Humans; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D007963:Leukocytes, Mononuclear; D016133:Polymerase Chain Reaction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
references.citation: J Exp Med. 2004 Oct 4;200(7):927-34
references.pmid: 15466623
references.citation: J Immunol. 2009 May 1;182(9):5570-85
references.pmid: 19380805
references.citation: Blood. 1997 Feb 15;89(4):1288-98
references.pmid: 9028952
references.citation: J Exp Med. 2008 Jun 9;205(6):1331-42
references.pmid: 18519648
references.citation: Curr Opin Immunol. 2008 Dec;20(6):632-8
references.pmid: 18848883
references.citation: J Biol Chem. 1998 Aug 21;273(34):21769-76
references.pmid: 9705314
references.citation: J Exp Med. 2006 Feb 20;203(2):393-400
references.pmid: 16446381
references.citation: J Exp Med. 2002 Feb 18;195(4):529-34
references.pmid: 11854365
references.citation: Immunology. 2001 Jun;103(2):179-87
references.pmid: 11412305
references.citation: Annu Rev Immunol. 2009;27:267-85
references.pmid: 19302041
references.citation: J Immunol. 2005 Mar 15;174(6):3454-60
references.pmid: 15749880
references.citation: J Exp Med. 2002 Feb 4;195(3):383-9
references.pmid: 11828014
references.citation: Blood. 2006 May 15;107(10):3967-75
references.pmid: 16439679
references.citation: J Immunol. 2007 Oct 1;179(7):4929-38
references.pmid: 17878393
references.citation: J Immunol. 2007 Jul 1;179(1):13-9
references.pmid: 17579014
references.citation: Int Immunol. 1998 Mar;10(3):341-6
references.pmid: 9576622
references.citation: J Immunol. 2008 Jan 15;180(2):800-8
references.pmid: 18178818
references.citation: Immunology. 1996 Jun;88(2):174-82
references.pmid: 8690448
references.citation: Ann N Y Acad Sci. 1995 Sep 29;764:384-96
references.pmid: 7486552
references.citation: J Immunol. 1995 May 1;154(9):4526-35
references.pmid: 7722307
references.citation: Mol Immunol. 2007 Mar;44(9):2173-83
references.pmid: 17196657
references.citation: J Clin Invest. 2004 Apr;113(8):1188-201
references.pmid: 15085198
references.citation: J Biol Chem. 2007 Mar 9;282(10):7405-15
references.pmid: 17197448
references.citation: Science. 2003 Sep 5;301(5638):1374-7
references.pmid: 12920303
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
references.pmid: 18503082
references.citation: Immunology. 2001 Mar;102(3):273-80
references.pmid: 11298825
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1166-70
references.pmid: 11158612
references.citation: Blood. 2002 Apr 1;99(7):2562-8
references.pmid: 11895794
references.citation: J Exp Med. 1995 Aug 1;182(2):559-66
references.pmid: 7629512
references.citation: J Exp Med. 2009 Nov 23;206(12):2659-69
references.pmid: 19917772
references.citation: Immunity. 2002 Sep;17(3):329-39
references.pmid: 12354385
references.citation: Blood. 2004 Dec 1;104(12):3647-54
references.pmid: 15191950
references.citation: J Exp Med. 2000 Feb 7;191(3):485-94
references.pmid: 10662794
references.citation: Res Immunol. 1997 May;148(4):267-76
references.pmid: 9300533
references.citation: Methods Mol Biol. 1999;112:531-52
references.pmid: 10027275
references.citation: J Exp Med. 2003 Apr 7;197(7):939-45
references.pmid: 12682112
references.citation: J Immunol. 2009 Sep 1;183(5):3237-48
references.pmid: 19667096
references.citation: Nature. 1996 Aug 1;382(6590):462-6
references.pmid: 8684487
references.citation: J Exp Med. 2008 Sep 1;205(9):2033-42
references.pmid: 18695003
references.citation: J Immunol. 2003 Jan 1;170(1):55-63
references.pmid: 12496383
references.citation: J Exp Med. 1994 Jul 1;180(1):329-39
references.pmid: 8006591