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

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 differentiatio...

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Bibliographic Details
Published in:Blood 2006-02, Vol.107 (3), p.1085-1091
Main Authors: Fornek, Jamie L., Tygrett, Lorraine T., Waldschmidt, Thomas J., Poli, Valeria, Rickert, Robert C., Kansas, Geoffrey S.
Format: Article
Language:English
Subjects:
Animals
Antigens, CD19 - immunology
Biological and medical sciences
Cell Differentiation - genetics
Cell Differentiation - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Immunoglobulin Isotypes - immunology
Integrases - genetics
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Macrophages - immunology
Mice
Mice, Knockout
Neutrophils - immunology
Plasma Cells - immunology
STAT3 Transcription Factor - deficiency
STAT3 Transcription Factor - immunology
T-Lymphocytes - immunology
Viral Proteins - genetics
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Summary: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 (Stat3fl/flCD19Cre/+). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3fl/flCD19Cre/+ mice. Strikingly, Stat3fl/flCD19Cre/+ 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 Stat3fl/flCD19Cre/+ 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-07-2871