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Zhixin Jing, Mark McCarron, David R Fooksman, Role of peptide-MHCII complexes in germinal center B cell selection and plasma cell differentiation, The Journal of Immunology, Volume 204, Issue 1_Supplement, May 2020, Page 71.4, https://doi.org/10.4049/jimmunol.204.Supp.71.4
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Abstract
Germinal center (GC) selection is critical for generating affinity-matured antibodies in T-cell-dependent immune responses. Despite the essential help follicular T cells provide to GC B cells, it is unclear how GC B cell fate decisions are made. Although cognate peptide-MHCII (pMHCII) is critical for T cell help, how pMHCII density directly contributes to B cell selection and cell fate remain unclear. The a-DEC205-OVA (dec) model system has been widely used to interrogate GC B selection, by enhancing selection of WT (Ly75+/+) B cells over untargeted Ly75−/− (KO) B cells. However, under these conditions, it is unclear what the fate of B cells presenting intermediate levels of pMHCII is and whether T cell help is indeed limited.
To investigate these questions, we used Ly75+/− (DEC-het) B cells, which expressed intermediate levels (~50%) of surface DEC205 protein compared to WT B cells, and presented proportional amount of OVA peptide after dec treatment. Using competitive transfers, we found that WT B cells expanded two-fold more than DEC-het B cells. This 2-fold difference in expansion was maintained at a wide range of dec administration, indicating that in vivo, T cells can distinguish different densities of pMHCII on multiple B cells in the same GC and respond proportionally. Surprisingly, we found that upon dec stimulation, both WT and DEC-het GC B cells were equally capable of differentiating into plasma cells, suggesting that pMHCII density does not control B cell fate directly. Blocking of CD40 signaling removed the two-fold advantage of WT over DEC-het B cells during selection after dec treatment, suggesting CD40 signaling is proportional to pMHCII density. These results provide new interpretations of how GC selection occurs in vivo.
