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PMID: 18513163 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Dlk1 influences differentiation and function of B lymphocytes.

Stem cells and development ·Vol. 17 ·No. 3 ·2008-06-00 ·Pages 495-507

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

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.

MeSH Terms
Animals Antibody Formation/immunology B-Lymphocytes/cytology,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
Chemicals
Calcium-Binding Proteins Dlk1 protein, mouse Immunoglobulins Intercellular Signaling Peptides and Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Raghunandan Ramadevi
Cellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Ruiz-Hidalgo Maria
Jia Yifeng
Ettinger Rachael
Rudikoff Eva
Riggins Patrick
Farnsworth Richard
Tesfaye Abeba
Laborda Jorge
Bauer Steven R
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Article Info
Journal
Stem cells and development
Abbr.
Stem Cells Dev
ISSN
1547-3287
DOI
10.1089/scd.2007.0102
Published
2008-06-00
Pages
495-507
Language
English
Region
United States
NLM ID
101197107
PMCID
PMC3189718
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1089/scd.2007.0102 PMC Full Text View journal details
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