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Published online before print July 14, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1205740

Received for publication December 17, 2005.
Revised March 29, 2006.
Accepted for publication April 13, 2006.

Article

Terminal B cell differentiation is skewed by deregulated interleukin-6 secretion in ₂ integrin-deficient mice

Thorsten Peters ^*, Wilhelm Bloch , Claudia Wickenhauser , Samir Tawadros , Tsvetelina Oreshkova ^*, Daniel Kess ^*, Thomas Krieg ^¶, Werner Müller ^||, and Karin Scharffetter-Kochanek ^*@

*Department of Dermatology and Allergic Diseases, University of Ulm, Germany; Institute of Pathology and Departments of Medical Hematology and Oncology and ^¶Dermatology and Center for Molecular Medicine (ZMMK), University of Cologne, Germany; Department for Molecular and Cellular Sports Medicine, Institute of Circulation Research and Sports Medicine, Cologne, Germany; and ^||Department of Experimental Immunology, Society for Biotechnological Research (GBF), Braunschweig, Germany

^@ To whom correspondence should be addressed. E-mail: karin.scharffetter-kochanek{at}medizin.uni-ulm.de.

	Abstract

Absence of the common chain (CD18) of ₂ integrins leads to leukocyte-adhesion deficiency type-1 (LAD1) in humans. Mice with a CD18 null mutation suffer from recurrent bacterial infections, impaired wound healing, and skin ulcers, closely resembling human LAD1. Previous findings in CD18^-/- mice demonstrated a skewed terminal B cell differentiation with plasmacytosis and elevated serum immunoglobulin G (IgG). As interleukin-6 (IL-6) is a potent enhancer of plasma cell formation and Ig secretion, we assessed IL-6 serum levels of CD18^-/- and wild-type (WT) mice kept under a conventional or barrier facility or specific pathogen-free (SPF) conditions. We detected an up to 20-fold increase in IL-6 in serum of CD18^-/- mice compared with WT controls when kept under conventional or barrier facility conditions, respectively. Under SPF conditions, no significant differences in terms of IL-6 serum levels were found between CD18^-/- and WT mice. However, histological alterations of secondary lymphoid tissues, plasmacytosis, abnormal plasmacytoid cells (Mott cells), and hypergammaglobulinemia persisted. To further analyze the role of IL-6 in these pathological alterations, we established a CD18^-/- IL-6^-/- double-deficient mouse mutant. In these mice, serum IgG levels were normal, and the altered plasma cell phenotype, including Mott cells, was no longer detectable. The CD18^-/- IL-6^-/- double-deficient mouse model thus demonstrated that IL-6 is responsible for parts of the phenotype seen in the CD18^-/- mouse mutants. It may be of interest to examine human leukocyte-adhesion deficiency type-1 patients closer and search for pathological changes possibly induced via overproduction of IL-6.

Key Words: hypergammaglobulinemia • proinflammatory cytokines • Mott cells • animal models

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