Terminal B cell differentiation is skewed by deregulated interleukin-6 secretion in β2 integrin-deficient mice

Thorsten Peters, Wilhelm Bloch, Claudia Wickenhauser, Samir Tawadros, Tsvetelina Oreshkova, Daniel Kess, Thomas Krieg, Werner Müller, Karin Scharffetter-Kochanek

    Research output: Contribution to journalArticlepeer-review


    Absence of the common β chain (CD18) of β2 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. © Society for Leukocyte Biology.
    Original languageEnglish
    Pages (from-to)599-607
    Number of pages8
    JournalJournal of Leukocyte Biology
    Issue number3
    Publication statusPublished - Sept 2006


    • Animal models
    • Hypergammaglobulinemia
    • Mott cells
    • Proinflammatory cytokines


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