TY - JOUR
T1 - Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells
AU - Fornek, Jamie L.
AU - Tygrett, Lorraine T.
AU - Waldschmidt, Thomas J.
AU - Poli, Valeria
AU - Rickert, Robert C.
AU - Kansas, Geoffrey S.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=31544474862&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544474862&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-07-2871
DO - 10.1182/blood-2005-07-2871
M3 - Article
C2 - 16223771
AN - SCOPUS:31544474862
VL - 107
SP - 1085
EP - 1091
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -