Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength.

Jing Z., McCarron MJ., Dustin ML., Fooksman DR.

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.

DOI

10.1016/j.celrep.2022.110763

Type

Journal article

Journal

Cell Rep

Publication Date

03/05/2022

Volume

39

Keywords

B1-8, CD40, CP: Immunology, DEC205, OT-2, OVA, T follicular helper cells, germinal center, intravital imaging, photoactivation, plasmablast, B-Lymphocytes, CD40 Ligand, Cell Differentiation, Germinal Center, Plasma Cells, T-Lymphocytes, Helper-Inducer

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