Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells

Jamie L Fornek; Lorraine T Tygrett; Thomas J Waldschmidt; Valeria Poli; Robert C Rickert; Geoffrey S Kansas

doi:10.1182/blood-2005-07-2871

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Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells

Journal article

Open access

Peer reviewed

Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells

Jamie L Fornek, Lorraine T Tygrett, Thomas J Waldschmidt, Valeria Poli, Robert C Rickert and Geoffrey S Kansas

Blood, Vol.107(3), pp.1085-1091

02/01/2006

DOI: 10.1182/blood-2005-07-2871

PMCID: PMC1895906

PMID: 16223771

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Abstract

Stat proteins are latent cytoplasmic transcription factors that are crucial in many aspects of mammalian development. In the immune system, Stat3 has distinct roles in T-cell, neutrophil, and macrophage function, but a role for Stat3 in B-cell development, particularly in the terminal differentiation of B cells into antibody-secreting plasma cells, has never been directly tested. In this study, we used the Cre/lox system to generate a mouse strain in which Stat3 was conditionally deleted in the B-cell lineage (Stat3(fl/fl)CD19(Cre/+)). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3(fl/fl)CD19(Cre/+) mice. Strikingly, Stat3(fl/fl)CD19(Cre/+) mice displayed profound defects in T-dependent (TD) IgG responses, but normal TD IgM, IgE, and IgA responses and T-independent (TI) IgM and IgG3 responses. In addition, germinal center (GC) formation, isotype switching, and generation of memory B cells, including IgG+ memory cells, were all intact in Stat3(fl/fl)CD19(Cre/+) mice, indicating that the requirement for Stat3 was limited to plasma cell differentiation. These results demonstrate a profound yet highly selective role for Stat3 in TD IgG plasma cell differentiation, and therefore represent a unique example of a transcription factor regulating isotype-specific terminal B-cell differentiation.

Neutrophils - immunology

Viral Proteins - genetics

Mice, Knockout

Cell Differentiation - genetics

Cell Differentiation - immunology

Animals

STAT3 Transcription Factor - deficiency

Immunoglobulin Isotypes - immunology

T-Lymphocytes - immunology

Mice

STAT3 Transcription Factor - immunology

Integrases - genetics

Macrophages - immunology

Antigens, CD19 - immunology

Plasma Cells - immunology

Details

Title: Subtitle: Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells
Creators: Jamie L Fornek - Department of Microbiology-Immunology, Feinberg School of Medicine of Northwestern University, Chicago, IL 60611, USA
Lorraine T Tygrett
Thomas J Waldschmidt
Valeria Poli
Robert C Rickert
Geoffrey S Kansas
Resource Type: Journal article
Publication Details: Blood, Vol.107(3), pp.1085-1091
Publisher: United States
DOI: 10.1182/blood-2005-07-2871
PMID: 16223771
PMCID: PMC1895906
ISSN: 0006-4971
eISSN: 1528-0020
Grant note: AA014400 / NIAAA NIH HHS GM08061 / NIGMS NIH HHS
Language: English
Date published: 02/01/2006
Academic Unit: Pathology
Record Identifier: 9984047704802771

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