Elevated frequencies of activated memory B cells in multiple sclerosis are reset to healthy control levels after B cell depletion with Ocrelizumab.

In multiple sclerosis (MS) the B cell depleting drug ocrelizumab has shown high efficacy in reducing inflammatory activity. Its mechanism of action is unclear due to B cell subset complexity and unknown roles in pathogenesis. Here, we comprehensively phenotyped and quantitated peripheral blood B cell subsets before and after ocrelizumab infusion to gain insight into the fate of B cell subsets with pathogenic potential.

Myeloperoxidase as a Marker to Differentiate Mouse Monocyte/Macrophage Subsets.

Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from the yolk sac/fetal liver that populate tissues for life. Other tissue macrophages derive from monocytes that differentiate in the bone marrow and circulate through tissues via the blood and lymphatics.

Neutrophil-Derived Myeloperoxidase Facilitates Both the Induction and Elicitation Phases of Contact Hypersensitivity.

Background: Allergic contact dermatitis (ACD) is a common skin disorder affecting an estimated 15-20% of the general population. The mouse model of ACD is contact hypersensitivity (CHS), which consists of two phases: induction and elicitation. Although neutrophils are required for both CHS disease phases their mechanisms of action are poorly understood.

Discovery and Function of B-Cell IgD Low (BD) B Cells in Immune Tolerance.

It is now appreciated that in addition to their role in humoral immunity, B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses. The concept of B-cell regulation became well recognized when mice deficient in B cells due to genetic disruption were shown to be refractory to recovery from the signs of experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. This seminal study spurred the search for B-cell regulatory phenotypes and mechanisms of action.

Mature IgD B cells maintain tolerance by promoting regulatory T cell homeostasis.

A number of different B cell subsets have been shown to exhibit regulatory activity using a variety of mechanisms to attenuate inflammatory diseases. Here we show, using anti-CD20-mediated partial B cell depletion in mice, that a population of mature B cells distinguishable by IgD expression maintains tolerance by, at least in part, promoting CD4Foxp3 regulatory T cell homeostatic expansion via glucocorticoid-induced tumor necrosis factor receptor ligand, or GITRL. Cell surface phenotyping, transcriptome analysis and developmental study data show that B cells expressing IgD at a low level (BD) are a novel population of mature B cells that emerge in the spleen from the transitional-2 stage paralleling the differentiation of follicular B cells.