| Abstract: |
Upon antigen (Ag) encounter, B cells require T-cell help to enter the germinal center (GC). They obtain this help by presenting Agderived peptides onMHC 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. |
| Keywords: |
nonhuman; antigen expression; animal cell; mouse; animals; mice; mice, knockout; animal experiment; cell population; mice, inbred c57bl; b lymphocyte; b-lymphocytes; mice, transgenic; germinal center; antigen presentation; major histocompatibility antigen class 2; recombinant proteins; adoptive transfer; t-lymphocytes, helper-inducer; adaptive immunity; histocompatibility antigens class ii; antigen processing; hla do antigen; phenylacetates; follicular helper t cells; h2-m; hla-do; mice, congenic; nitrophenols; receptors, antigen, b-cell
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