H2-O, a MHC class II-like protein, sets a threshold for B-cell entry into germinal centers.
Upon antigen (Ag) encounter, B cells require T-cell help to enter the germinal center (GC). They obtain this help by presenting Ag-derived peptides on MHC class II (MHCII) for recognition by the T-cell receptor (TCR) of CD4(+) T cells. Peptides are loaded onto MHCII in endosomal compartments in a process catalyzed by the MHCII-like protein H2-M (HLA-DM in humans). This process is modulated by another MHCII-like protein, H2-O (HLA-DO in humans). H2-O is a biochemical inhibitor of peptide loading onto MHCII; however, on the cellular level, it has been shown to have varying effects on Ag presentation. Thus, the function of H2-O in the adaptive immune response remains unclear. Here, we examine the effect of H2-O expression on the ability of Ag-specific B cells to enter the GC. We show that when Ag specific WT and H2-O(-/-) B cells are placed in direct competition, H2-O(-/-) B cells preferentially populate the GC. This advantage is confined to Ag-specific B cells and is due to their superior ability to obtain Ag-specific T-cell help when T-cell help is limiting. Overall, our work shows that H2-O expression reduces the ability of B cells to gain T-cell help and participate in the GC reaction.
Draghi
Nicole A
NA
Biochemistry and Structural Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Denzin
Lisa K
LK
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
C416186:H-2O antigen; D000949:Histocompatibility Antigens Class II; D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; C026242:4-hydroxy-5-nitrophenyl acetic acid
Immunol Res. 1999;20(3):195-205
10741860
Immunol Cell Biol. 1998 Feb;76(1):34-40
9553774
Immunity. 1995 Aug;3(2):197-205
7648393
Immunol Rev. 2005 Oct;207:279-92
16181343
J Exp Med. 2002 Apr 15;195(8):1063-9
11956297
Curr Opin Immunol. 2009 Jun;21(3):266-73
19502021
Nature. 1995 Jun 29;375(6534):802-6
7596415
Cell. 1995 Jul 14;82(1):155-65
7606781
EMBO J. 1996 Sep 16;15(18):4817-24
8890155
Annu Rev Immunol. 1997;15:821-50
9143708
Nat Immunol. 2002 Jun;3(6):570-5
12021782
Nat Immunol. 2002 Apr;3(4):399-406
11896394
J Clin Invest. 2010 Apr;120(4):1324-36
20200448
Immunity. 2009 Apr 17;30(4):599-609
19303334
J Exp Med. 2002 Apr 15;195(8):1053-62
11956296
J Immunol. 2003 Sep 1;171(5):2331-7
12928379
Science. 1997 Oct 3;278(5335):106-9
9311912
J Immunol. 2004 Aug 1;173(3):1549-60
15265882
Nat Rev Immunol. 2008 Jan;8(1):22-33
18097447
Immunity. 1997 Aug;7(2):197-208
9285405
Immunity. 2007 Aug;27(2):190-202
17723214
Curr Biol. 1997 Dec 1;7(12):950-7
9382849
Immunity. 1995 Nov;3(5):561-72
7584146
Immunity. 1998 Feb;8(2):233-43
9492004
Annu Rev Immunol. 2000;18:113-42
10837054
J Immunol. 2007 Feb 1;178(3):1488-97
17237397
Annu Rev Immunol. 1993;11:331-60
8476565
Eur J Immunol. 2000 Oct;30(10):2871-80
11069069