Bone infection and inflammation leads to the infiltration of immune cells at the site of infection, where they modulate the differentiation and function of osteoclasts and osteoblasts by the secretion of various cytokines and signal mediators. In recent years, there has been a tremendous effort to understand the cells involved in these interactions and the complex pathways of signal transduction and their ultimate effect on bone metabolism. These crosstalk mechanisms between the bone and immune system finally emerged, forming a new field of research called osteoimmunology. Diseases falling into the category of osteoimmunology, such as osteoporosis, periodontitis, and bone infections are considered to have a significant implication in mortality and morbidity of patients, along with affecting their quality of life. There is a much-needed research focus in this new field, as the reported data on the immunomodulation of immune cells and their signaling pathways seems to have promising therapeutic benefits for patients.

B cells have emerged as an important immune cell type that can be targeted for therapy in multiple sclerosis (MS). Depleting B cells with anti-CD20 antibodies is effective in treating MS. Yet, atacicept treatment, which blocks B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), two cytokines important for B cell development and function, paradoxically increases disease activity in MS patients. The reason behind the failure of atacicept is not well understood. The stark differences in clinical outcomes with these therapies demonstrate that B cells have both inflammatory and anti-inflammatory functions in MS. In this review, we summarize the importance of B cells in MS and discuss the different B cell subsets that perform inflammatory and anti-inflammatory functions and how therapies modulate B cell functions in MS patients. Additionally, we discuss the potential anti-inflammatory functions of BAFF and APRIL on MS disease.

Summary: Chronic bone infection is associated with bone resorption. From animal studies, CD3/CD28-activated T cells are known to enhance osteoclastogenesis and bone resorption. Because CD28 is expressed constitutively on T cells and its expression is down-regulated by chronic exposure to the inflammatory environment, we characterized co-stimulatory molecule expression on T cells from chronically infected patients. We used cytofluorometric techniques to phenotypically characterize T cells, its co-stimulatory molecules and perforin secretion from infected and non-infected human bones. Chronic bone infection was defined as infection lasting for more than a month. We show a higher T cell activation [human leucocyte antigen D-related (HLA-DR+)] in infected compared to non-infected bones: median being 16 versus 7%, P = 0·009 for CD4 T cells, and 33 versus 15%, P = 0·038 for CD8 T cells, respectively. However, T cell proliferation (Ki67+) was lower for CD8 T cells in infected bones: 26 versus 34%, P = 0·045. In contrast, we detected no difference in apoptosis and regulatory T cells. In infected bone, we found higher CD28-negative CD4+ T cells compared to non-infected bone: 20 versus 8%, respectively (P = 0·005); this T cell subset had higher CD11b expression and perforin secretion. Chronically infected human bones are characterized by an increase of CD28-negative CD4+ T cells, indicating long-term activated cells with cytotoxic ability. Therefore, this alteration of co-stimulatory molecules may modify interactions with osteoclasts and impact bone resorption.