@article{dc0da8f516054b24927fc8c136857e97,
title = "Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength",
abstract = "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.",
keywords = "B1-8, CD40, CP: Immunology, DEC205, OT-2, OVA, T follicular helper cells, germinal center, intravital imaging, photoactivation, plasmablast",
author = "Zhixin Jing and McCarron, {Mark J.} and Dustin, {Michael L.} and Fooksman, {David R.}",
note = "Funding Information: This work was supported by NIH R01AI72529 (D.R.F. and M.L.D.), HL141491 (D.R.F. Z.J. and M.J.M.), S10 RR023704 (M.L.D.), the Kennedy Trust for Rheumatology Research (M.L.D.), and the Albert Einstein NCI Cancer Center P30CA013330. We would like to thank Michel Nussenzweig. Experiments were conceived by D.R.F. and M.L.D. D.R.F. contributed to experiments in Figures 3 and S2. M.J.McC. contributed to experiments in Figures 1, 2, and 3. Z.J. conducted the remaining and majority of experiments. D.R.F. and Z.J. wrote the manuscript and all authors contributed to editing. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: This work was supported by NIH R01AI72529 (D.R.F. and M.L.D.), HL141491 (D.R.F., Z.J., and M.J.M.), S10 RR023704 (M.L.D.), the Kennedy Trust for Rheumatology Research (M.L.D.), and the Albert Einstein NCI Cancer Center P30CA013330 . We would like to thank Michel Nussenzweig. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = may,
day = "3",
doi = "10.1016/j.celrep.2022.110763",
language = "English (US)",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}