Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength
Summary: 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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722005277 |
| _version_ | 1818242972083290112 |
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| author | Zhixin Jing Mark J. McCarron Michael L. Dustin David R. Fooksman |
| author_facet | Zhixin Jing Mark J. McCarron Michael L. Dustin David R. Fooksman |
| author_sort | Zhixin Jing |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-12T13:53:43Z |
| format | Article |
| id | doaj.art-5dffdefe8835446eb1400765d2c303f5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T13:53:43Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5dffdefe8835446eb1400765d2c303f52022-12-22T00:22:30ZengElsevierCell Reports2211-12472022-05-01395110763Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strengthZhixin Jing0Mark J. McCarron1Michael L. Dustin2David R. Fooksman3Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USAKennedy Institute of Rheumatology, University of Oxford, Oxford OX3-7FY, UKDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124722005277CP: Immunology |
| spellingShingle | Zhixin Jing Mark J. McCarron Michael L. Dustin David R. Fooksman Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength Cell Reports CP: Immunology |
| title | Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength |
| title_full | Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength |
| title_fullStr | Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength |
| title_full_unstemmed | Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength |
| title_short | Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength |
| title_sort | germinal center expansion but not plasmablast differentiation is proportional to peptide mhcii density via cd40 cd40l signaling strength |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722005277 |
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