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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.

Titel:	Isotype-specific plasma cells express divergent transcriptional programs.
Autor/in / Beteiligte Person:	Higgins, BW ; Shuparski, AG ; Miller, KB ; Robinson, AM ; McHeyzer-Williams, LJ ; McHeyzer-Williams, MG
Link:	Full Text Finder (Volltext)
Zeitschrift:	Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-06-21), Heft 25, S. e2121260119
Veröffentlichung:	Washington, DC : National Academy of Sciences, 2022
Medientyp:	academicJournal
ISSN:	1091-6490 (electronic)
DOI:	10.1073/pnas.2121260119
Schlagwort:	Animals Antigens Immunoglobulin G genetics Immunoglobulin M Mice Single-Cell Analysis T-Lymphocytes, Helper-Inducer Cell Differentiation Germinal Center Plasma Cells cytology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural Language: English [Proc Natl Acad Sci U S A] 2022 Jun 21; Vol. 119 (25), pp. e2121260119. <i>Date of Electronic Publication: </i>2022 Jun 15. MeSH Terms: Cell Differentiation* ; Germinal Center* ; Plasma Cells* / cytology ; Animals ; Antigens ; Immunoglobulin G / genetics ; Immunoglobulin M ; Mice ; Single-Cell Analysis ; T-Lymphocytes, Helper-Inducer References: Sci Rep. 2016 Mar 24;6:23682. (PMID: 27009467) ; J Exp Med. 2000 Apr 3;191(7):1149-66. (PMID: 10748233) ; Immunity. 2015 Sep 15;43(3):541-53. (PMID: 26320660) ; Nat Immunol. 2015 Jun;16(6):663-73. (PMID: 25894659) ; Science. 2014 Aug 29;345(6200):1058-62. (PMID: 25170154) ; Immunity. 2014 Oct 16;41(4):529-42. (PMID: 25367570) ; Biochem Biophys Res Commun. 2012 Sep 7;425(4):918-23. (PMID: 22906740) ; Immunity. 2018 Mar 20;48(3):556-569.e7. 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(PMID: 30778241) Grant Information: R01 AI040215 United States AI NIAID NIH HHS; R01 AI047231 United States AI NIAID NIH HHS; R01 AI071182 United States AI NIAID NIH HHS Contributed Indexing: Keywords: antibodies; isotype; plasma cell; single-cell RNA-seq Substance Nomenclature: 0 (Antigens) ; 0 (Immunoglobulin G) ; 0 (Immunoglobulin M) Entry Date(s): Date Created: 20220615 Date Completed: 20220617 Latest Revision: 20240214 Update Code: 20240214 PubMed Central ID: PMC9231473

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Isotype-specific plasma cells express divergent transcriptional programs.