Programming isotype specific plasma cell differentiation
Abstract 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. Using integrated single cell strategies, we reveal conserved and divergent components of the rapid effector phase of antigen-specific IgM+versus inflammation modulating programs dictated by IgG2a/b+PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC inhibitory IgG1+and 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 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..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 08. Jan. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Higgins, Brett W. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.08.31.458458 |
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| PPN (Katalog-ID): |
XBI032496923 |
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| 520 | |a Abstract 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. Using integrated single cell strategies, we reveal conserved and divergent components of the rapid effector phase of antigen-specific IgM+versus inflammation modulating programs dictated by IgG2a/b+PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC inhibitory IgG1+and 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 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. | ||
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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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