Dlk1 influences differentiation and function of B lymphocytes.
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.
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.
Ramadevi
R
Raghunandan
Maria
M
Ruiz-Hidalgo
Yifeng
Y
Jia
Rachael
R
Ettinger
Eva
E
Rudikoff
Patrick
P
Riggins
Richard
R
Farnsworth
Abeba
A
Tesfaye
Jorge
J
Laborda
Steven R
SR
Bauer
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D018390:Gene Targeting; D006706:Homeostasis; D007136:Immunoglobulins / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D007136:Immunoglobulins; D036341:Intercellular Signaling Peptides and Proteins