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

Absence of the common β chain (CD18) of β 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.