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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1085-1091.
Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-07-2871.
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IMMUNOBIOLOGY
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
From the Department of Microbiology-Immunology, Feinberg School of Medicine of Northwestern University, Chicago, IL; the Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA; the Department of Genetics, Biology, and Biochemistry, University of Turin, Turin, Italy; and the Infectious and Inflammatory Disease Center, The Burnham Institute, La Jolla, CA.
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.
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