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T follicular helper (TFH) cells promote expansion of germinal center (GC) B cells and plasma cell differentiation. Whether cognate peptide-MHCII (pMHCII) density instructs selection and cell fate decisions in a quantitative manner remains unclear. Using αDEC205-OVA to differentially deliver OVA peptides to GC B cells on the basis of DEC205 allelic copy number, we find DEC205+/+ B cells take up 2-fold more antigen than DEC205+/- cells, leading to proportional TFH cell help and B cell expansion. To validate these results, we establish a caged OVA peptide, which is readily detected by OVA-specific TFH cells after photo-uncaging. In situ uncaging of peptides leads to multiple serial B-T contacts and cell activation. Differential CD40 signaling, is both necessary and sufficient to mediate 2-fold differences in B cell expansion. While plasmablast numbers are increased, pMHCII density does not directly control the output or quality of plasma cells. Thus, we distinguish the roles TFH cells play in expansion versus differentiation.

Original publication

DOI

10.1016/j.celrep.2022.110763

Type

Journal article

Journal

Cell reports

Publication Date

05/2022

Volume

39

Addresses

Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Keywords

Germinal Center, B-Lymphocytes, Plasma Cells, T-Lymphocytes, Helper-Inducer, CD40 Ligand, Cell Differentiation