Isotype-specific plasma cells express divergent transcriptional programs
Antibodies are produced across multiple isotypes with distinct properties that coordinate initial antigen clearance and confer long-term antigen-specific immune protection. Here, we interrogate the molecular programs of isotype-specific murine plasma cells (PC) following helper T cell-dependent immunization and within established steady-state immunity. We developed a single-cell-indexed and targeted molecular strategy to dissect conserved and divergent components of the rapid effector phase of antigen-specific IgM+ versus inflammation-modulating programs dictated by type 1 IgG2a/b+ PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC type 2 inhibitory IgG1+ and type 1 inflammatory IgG2a/b+ PC to direct long-term cellular function. In the steady state, two subsets of IgM+ and separate IgG2b+ PC programs clearly segregate from splenic type 3 IgA+ PC programs that emphasize mucosal barrier protection. These diverse isotype-specific molecular pathways of PC differentiation control complementary modules of antigen clearance and immune protection that could be selectively targeted for immunotherapeutic applications and vaccine design.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 25 vom: 21. Juni, Seite e2121260119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Higgins, Brett W [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies |
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| Anmerkungen: |
Date Completed 17.06.2022 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2121260119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM342261665 |
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| 245 | 1 | 0 | |a Isotype-specific plasma cells express divergent transcriptional programs |
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| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antibodies are produced across multiple isotypes with distinct properties that coordinate initial antigen clearance and confer long-term antigen-specific immune protection. Here, we interrogate the molecular programs of isotype-specific murine plasma cells (PC) following helper T cell-dependent immunization and within established steady-state immunity. We developed a single-cell-indexed and targeted molecular strategy to dissect conserved and divergent components of the rapid effector phase of antigen-specific IgM+ versus inflammation-modulating programs dictated by type 1 IgG2a/b+ PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC type 2 inhibitory IgG1+ and type 1 inflammatory IgG2a/b+ PC to direct long-term cellular function. In the steady state, two subsets of IgM+ and separate IgG2b+ PC programs clearly segregate from splenic type 3 IgA+ PC programs that emphasize mucosal barrier protection. These diverse isotype-specific molecular pathways of PC differentiation control complementary modules of antigen clearance and immune protection that could be selectively targeted for immunotherapeutic applications and vaccine design | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 4 | |a isotype | |
| 650 | 4 | |a plasma cell | |
| 650 | 4 | |a single-cell RNA-seq | |
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| 700 | 1 | |a Shuparski, Andrew G |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Karen B |e verfasserin |4 aut | |
| 700 | 1 | |a Robinson, Amanda M |e verfasserin |4 aut | |
| 700 | 1 | |a McHeyzer-Williams, Louise J |e verfasserin |4 aut | |
| 700 | 1 | |a McHeyzer-Williams, Michael G |e verfasserin |4 aut | |
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