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Stem Cells Dev 2008 Jun;17(3):495-507

Dlk1 Influences Differentiation and Function of B Lymphocytes.

Raghunandan R, Ruiz-Hidalgo M, Jia Y, Ettinger R, Rudikoff E, Riggins P, Farnsworth R, Tesfaye A, Laborda J, Bauer SR

Bauer, SR (reprint author), FDA Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, NIH Bldg 29B Room 2NN10,HFM-740,1401 Rockville Pi, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA Univ Castilla La Mancha, Biochem & Mol Biol Branch, Med Sch Reg Ctr Biomed Invest CRIB, Albacete, Spain NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA


The Dlk1 (delta-like-1) gene is a member of the epidermal growth factor (EGF)-like homeotic gene family. It influences cell-cell interactions between stromal cells and pro-B cells in vitro. To define the in vivo role of the dlk protein in B cell development, we established a Dlk1(/) mouse model. In spleens of Dlk1(/) mice, transitional B cell numbers were increased and the ratio between transitional B cell subsets was altered. Numbers of follicular B cells decreased, while the number of marginal zone B cells and the size of the marginal zone were increased. Loss of dlk resulted in increased immunoglobulin G1 (IgG1) and IgG(3) in preimmune sera. Furthermore, there was an exaggerated primary T-dependent antigen-specific humoral immune response. In bone marrow, the lack of dlk led to increased numbers of the earliest B lineage cells in young mice without affecting numbers of later B lineage cells. In vitro experiments showed that lack of dlk on either stromal cells or pro-B cells caused changes in differentiation and proliferation of pro-B cells, suggesting that lack of dlk leads to changes in cell-cell interactions in the bone marrow microenvironment. These results show that dlk expression is essential for normal B cell development.

Category: Journal Article
PubMed ID: #18513163
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29