TY - JOUR
T1 - Vav proteins regulate the plasma cell program and secretory Ig production
AU - Stephenson, Linda M.
AU - Miletic, Ana V.
AU - Kloeppel, Tracie
AU - Kusin, Shana
AU - Swat, Wojciech
PY - 2006/12/15
Y1 - 2006/12/15
N2 - Plasma cell (PC) development is initiated following B cell activation and controlled by a B lymphocyte-induced maturation protein (Blimp)-1-dependent program involving the concerted action of several proplasma transcriptional regulators. However, the factors that control Blimp-1 expression remain largely unknown. In this context, mice deficient for all three of the Vav Family of proteins (Vavnull) develop substantial B cell populations, including marginal zone B cells, yet have a virtual absence of serum Igs, indicating that Vav may be specifically required in PC development and Ig production. We show in this study that mature marginal zone B cells from Vavnull mice proliferate following stimulation with TLR ligands but exhibit severe defects in PC differentiation and Ig secretion. Under conditions inducing PC differentiation, Vavnull B cells fail to efficiently induce Blimp-1, X box-binding protein-1, J chain, or secretory Ig μ transcripts but express IFN-regulatory factor-4 at levels similar to wild-type cells. These data indicate a previously unknown role for Vav as an upstream regulator of Blimp-1.
AB - Plasma cell (PC) development is initiated following B cell activation and controlled by a B lymphocyte-induced maturation protein (Blimp)-1-dependent program involving the concerted action of several proplasma transcriptional regulators. However, the factors that control Blimp-1 expression remain largely unknown. In this context, mice deficient for all three of the Vav Family of proteins (Vavnull) develop substantial B cell populations, including marginal zone B cells, yet have a virtual absence of serum Igs, indicating that Vav may be specifically required in PC development and Ig production. We show in this study that mature marginal zone B cells from Vavnull mice proliferate following stimulation with TLR ligands but exhibit severe defects in PC differentiation and Ig secretion. Under conditions inducing PC differentiation, Vavnull B cells fail to efficiently induce Blimp-1, X box-binding protein-1, J chain, or secretory Ig μ transcripts but express IFN-regulatory factor-4 at levels similar to wild-type cells. These data indicate a previously unknown role for Vav as an upstream regulator of Blimp-1.
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U2 - 10.4049/jimmunol.177.12.8620
DO - 10.4049/jimmunol.177.12.8620
M3 - Article
C2 - 17142761
AN - SCOPUS:33845397133
SN - 0022-1767
VL - 177
SP - 8620
EP - 8625
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -