Complex Organizational Defects of Fibroblast Architecture in the Mouse Spleen with Nkx2.3 Homeodomain Deficiency

Judit BOVÁRI1, Tamás CZÖMPÖLY1, Katinka OLASZ1, Hans-Henning ARNOLD2, Péter BALOGH1

1Department of Immunology & Biotechnology, Faculty of Medicine, University of Pécs, Pécs, Hungary
2Department of Cell & Molecular Biology, Institute of Biochemistry & Biotechnology, Technical University of Braunschweig, Braunschweig, Germany


The capacity of secondary lymphoid organs to provide suitable tissue environment for mounting immune responses is dependent on their compartmentalized stromal constituents, including distinct fibroblasts. In addition to various members of the tumor necrosis factor/lymphotoxin beta family as important morphogenic regulators of peripheral lymphoid tissue development, the formation of stromal elements of spleen is also influenced by the Nkx2.3 homeodomain transcription factor in a tissue-specific fashion. Here we extend our previous work on the role of Nkx2.3-mediated regulation in the development of spleen architecture by analyzing the structure of reticular fibroblastic meshwork of spleen in inbred Nkx2.3-deficient mice. Using immunohistochemistry and dual-label immunofluorescence we found both distributional abnormalities, manifested as poor reticular compartmentalization of T-zone and circumferential reticulum, and developmental blockade, resulting in the absence of a complementary fibroblast subpopulation of white pulp. The disregulated distribution of fibroblasts was accompanied with an increased binding of immunohistochemically detectable complement factor C4 by T-cell zone-associated reticular fibroblasts, distinct from follicular dendritic cells with inherently high-level expression of bound C4. These data indicate that the impact of Nkx2.3 gene deficiency on fibroblast ontogeny within the spleen extends beyond its distributional effects, and that the formation of various white pulp fibroblast subsets is differentially affected by the presence of Nkx2.3 activity, possibly also influencing their role in various immune functions linked with complement activation and deposition. Pathology & Oncology Research, Vol 13, Nr 3, 227-235, 2007

Key words: spleen; fibroblast heterogeneity; Nkx2.3

Received: Mar 27, 2007; accepted: Jul 20, 2007
Correspondence: Péter BALOGH, Department of Immunology & Biotechnology, Faculty of Medicine, University of Pécs, Szigeti út 12 Pécs H-7643, Hungary; Tel: +36 72 536-001/6524, Fax: +36 72 536-289; E-mail:

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