High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations.
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.
Wu
Yu-Chang
YC
Department of Immunobiology, King's College London School of Medicine, London, UK.
Kipling
David
D
Leong
Hui Sun
HS
Martin
Victoria
V
Ademokun
Alexander A
AA
Dunn-Walters
Deborah K
DK
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
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
J Exp Med. 2004 Oct 4;200(7):927-34
15466623
J Immunol. 2009 May 1;182(9):5570-85
19380805
Blood. 1997 Feb 15;89(4):1288-98
9028952
J Exp Med. 2008 Jun 9;205(6):1331-42
18519648
Curr Opin Immunol. 2008 Dec;20(6):632-8
18848883
J Biol Chem. 1998 Aug 21;273(34):21769-76
9705314
J Exp Med. 2006 Feb 20;203(2):393-400
16446381
J Exp Med. 2002 Feb 18;195(4):529-34
11854365
Immunology. 2001 Jun;103(2):179-87
11412305
Annu Rev Immunol. 2009;27:267-85
19302041
J Immunol. 2005 Mar 15;174(6):3454-60
15749880
J Exp Med. 2002 Feb 4;195(3):383-9
11828014
Blood. 2006 May 15;107(10):3967-75
16439679
J Immunol. 2007 Oct 1;179(7):4929-38
17878393
J Immunol. 2007 Jul 1;179(1):13-9
17579014
Int Immunol. 1998 Mar;10(3):341-6
9576622
J Immunol. 2008 Jan 15;180(2):800-8
18178818
Immunology. 1996 Jun;88(2):174-82
8690448
Ann N Y Acad Sci. 1995 Sep 29;764:384-96
7486552
J Immunol. 1995 May 1;154(9):4526-35
7722307
Mol Immunol. 2007 Mar;44(9):2173-83
17196657
J Clin Invest. 2004 Apr;113(8):1188-201
15085198
J Biol Chem. 2007 Mar 9;282(10):7405-15
17197448
Science. 2003 Sep 5;301(5638):1374-7
12920303
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W503-8
18503082
Immunology. 2001 Mar;102(3):273-80
11298825
Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1166-70
11158612
Blood. 2002 Apr 1;99(7):2562-8
11895794
J Exp Med. 1995 Aug 1;182(2):559-66
7629512
J Exp Med. 2009 Nov 23;206(12):2659-69
19917772
Immunity. 2002 Sep;17(3):329-39
12354385
Blood. 2004 Dec 1;104(12):3647-54
15191950
J Exp Med. 2000 Feb 7;191(3):485-94
10662794
Res Immunol. 1997 May;148(4):267-76
9300533
Methods Mol Biol. 1999;112:531-52
10027275
J Exp Med. 2003 Apr 7;197(7):939-45
12682112
J Immunol. 2009 Sep 1;183(5):3237-48
19667096
Nature. 1996 Aug 1;382(6590):462-6
8684487
J Exp Med. 2008 Sep 1;205(9):2033-42
18695003
J Immunol. 2003 Jan 1;170(1):55-63
12496383
J Exp Med. 1994 Jul 1;180(1):329-39
8006591