Editors' ChoiceInflammation

The skin-y on B cell subsets

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Science Translational Medicine  04 Nov 2015:
Vol. 7, Issue 312, pp. 312ec190
DOI: 10.1126/scitranslmed.aad5506

B cells go beyond antibody production to play an important role in immune defense, including antigen presentation, T cell activation, and cytokine secretion. But prior studies on psoriasis and atopic dermatitis—the two most common inflammatory skin diseases—have focused on the contribution of T cells to the immune dysregulation and barrier dysfunction that characterize these disorders. Studies in mice suggest that B cells are required for antigen-specific T cell activation—a hallmark of allergic disease—but in humans, the B-cell contribution to allergic skin disease is not well described. Now, Czarnowicki and colleagues quantify, in healthy controls versus patients with atopic dermatitis or psoriasis, the frequencies of several B cell subsets such as plasmablasts and naïve, memory, transitional, and activated B cells.

The authors showed that patients with atopic dermatitis had higher total B cell frequencies in peripheral blood (by flow cytometry detection of CD19+) and in lesional skin (by immunohistochemistry detection of CD20+), and disease severity correlated with CD20+ cell counts. Further characterization of the B cell compartment in these patients revealed that it housed fewer CD27 memory B cells relative to healthy controls, although IgE production was highest in this subset. This suggests that although there were fewer cells in this subset, they were more likely to affect the inflammatory phenotype. CD27+IgD (switched B cells; that is, those that have undergone maturation to switch their immunoglobulin receptors) and CD27+IgD+ (nonswitched) memory B cells displayed higher expression levels of the class II major histocompatibility complex HLA-DR relative to controls, suggesting that these cells are more likely to be activated by Th2 cells. Numbers of activated B cells correlated positively with the activation of skin-homing (CLA+) T cells and disease severity; correlation of activated T and B cell frequencies was not observed in patients with psoriasis or healthy control subjects.

These data illustrate that memory B cells are chronically activated in atopic dermatitis and suggest that this activation is important in maintaining T cell activation, which contributes to disease pathogenesis. B cell activation might then elicit higher levels of immunoglobulin class switching from IgM to IgE (a hallmark of the disorder), as measures of B cell activation correlated with IgE expression in memory B cells. The authors then examined B cell expression of CD23, a low-affinity IgE receptor involved in the augmentation of IgE synthesis, and found that it was higher in atopic dermatitis patients compared with patients with psoriasis or control subjects and correlated with disease severity. Last, the authors found that the frequency of CD19+CD27++CD38++ plasmablasts and levels of IgE expression by these cells were higher in the blood of atopic dermatitis patients relative to healthy controls.

Thus atopic dermatitis appears to be accompanied by systemic expansion of transitional and chronically activated CD27+ and IgE-expressing memory B cell and plasmablast subsets, and frequencies of these subsets correlate with increased IgE expression, T cell activation, and T cell memory responses. Together, these findings offer insight into how B cell differentiation and activation contribute to the pathogenesis of inflammatory diseases traditionally studied with a T cell focus. Further studies to explore the interplay of B and T cell differentiation and activation might elucidate mechanisms of disease initiation and progression as well as new therapy targets.

T. Czarnowicki et al., Diverse activation and differentiation of multiple B-cell subsets in patients with atopic dermatitis but not in patients with psoriasis. J. Allergy Clin. Immunol. 10.1016/j.jaci.2015.08.027 (2015). [Abstract]

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