First Author | Draghi NA | Year | 2010 |
Journal | Proc Natl Acad Sci U S A | Volume | 107 |
Issue | 38 | Pages | 16607-12 |
PubMed ID | 20807742 | Mgi Jnum | J:164357 |
Mgi Id | MGI:4833714 | Doi | 10.1073/pnas.1004664107 |
Citation | Draghi NA, et al. (2010) H2-O, a MHC class II-like protein, sets a threshold for B-cell entry into germinal centers. Proc Natl Acad Sci U S A 107(38):16607-12 |
abstractText | 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. |