title: H2-O, a MHC class II-like protein, sets a threshold for B-cell entry into germinal centers.
abstract: 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.
authors.affiliation: Biochemistry and Structural Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Draghi
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Denzin
mesh_terms: 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
chemical_list: 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
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