Dlk1 influences differentiation and function of B lymphocytes

Stem Cells Dev. 2008 Jun;17(3):495-507. doi: 10.1089/scd.2007.0102.

Abstract

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 IgG3 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Bone Marrow Cells / cytology
  • Calcium-Binding Proteins
  • Cell Differentiation*
  • Cell Lineage
  • Gene Targeting
  • Homeostasis
  • Immunoglobulins / immunology
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Lymphocyte Subsets / cytology
  • Mice
  • Spleen / cytology
  • Stem Cells / cytology
  • T-Lymphocytes / cytology

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Immunoglobulins
  • Intercellular Signaling Peptides and Proteins