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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

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 (Stat3fl/flCD19 Cre/+). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3 fl/flCD19Cre/+ mice. Strikingly, Stat3 fl/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/flCD19 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.

Original languageEnglish (US)
Pages (from-to)1085-1091
Number of pages7
JournalBlood
Volume107
Issue number3
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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