Vav proteins regulate the plasma cell program and secretory Ig production.
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 (Vav(null)) 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 Vav(null) mice proliferate following stimulation with TLR ligands but exhibit severe defects in PC differentiation and Ig secretion. Under conditions inducing PC differentiation, Vav(null) B cells fail to efficiently induce Blimp-1, X box-binding protein-1, J chain, or secretory Ig mu 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.
Stephenson
Linda M
LM
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Miletic
Ana V
AV
Kloeppel
Tracie
T
Kusin
Shana
S
Swat
Wojciech
W
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051567:Proto-Oncogene Proteins c-vav / Q000172:deficiency / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D007136:Immunoglobulins; C513258:Prdm1 protein, mouse; D051567:Proto-Oncogene Proteins c-vav; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1