Skin-Associated B Cells in Health and Inflammation

Abstract

Traditionally, the skin was believed to be devoid of B cells, and studies of the skin immune system have largely focused on other types of leukocytes. Exciting recent data show that B cells localize to the healthy skin of humans and other mammalian species with likely homeostatic functions in host defense, regulation of microbial communities, and wound healing. Distinct skin-associated B cell subsets drive or suppress cutaneous inflammatory responses with important clinical implications. Localized functions of skin-associated B cell subsets during inflammation comprise Ab production, interactions with skin T cells, tertiary lymphoid tissue formation, and production of proinflammatory cytokines but also include immunosuppression by providing IL-10. In this review, we delve into the intriguing new roles of skin-associated B cells in homeostasis and inflammation.

Beyond antibodies: B cells in Hidradenitis Suppurativa: Bystanders, contributors or therapeutic targets?

“…B cells are present in extremely low numbers in normal, uninflamed human skin biopsies [2‐3,5,11] . This low concentration in histological specimens masks the important role of B cells in innate cutaneous immunity [2,3,5] and is attributable to B cells continuously re‐circulating from cutaneous tissue to lymphoid organs [2] . The role of B cells in antibody production is an essential part of cutaneous homeostasis that is evolutionarily conserved amongst vertebrates, [5] providing a key contribution to cutaneous host defence.…”

“…The distribution of B cells within skin varies, with antibody secreting B cells in higher concentrations surrounding eccrine glands and hair follicles [1,2] . The number of antibody secreting B cells is independent of T cells and microbiota composition, suggesting re‐circulating B cells are an inherent part of cutaneous immunity [3,5] . The majority of our knowledge regarding regional cutaneous B‐cell density variation is extrapolated from murine or ovine studies [2,3] .…”

“…Cutaneous B cells are a heterogeneous population consisting of B1 (innate‐like) and B2 (conventional) B cells [5,6] . Compared with B‐cell distribution in lymphoid organs, B1 cells are enriched in skin whilst B2 cells have specific IgG subclasses which have led some authors to propose a skin‐specific subset of B cells (termed skin‐resident memory B cells) [3,11,14] although evidence of this subset in inflammatory skin disease remains controversial [9,10] .…”

“…Our understanding of the role of B cells in innate and adaptive immunity is rapidly evolving [2‐4] with acknowledgement of their complex multifaceted role in innate immunity through functions including antigen presentation, non‐specific antibody secretion, antigen presentation and cytokine secretion (Figure 1). [4‐6] …”

“…The majority of novel therapeutics of the past two decades were derived from our reasonably comprehensive understanding of T‐cell function in inflammatory disease [7] . Major disconnects between B‐cell function and cell surface markers, along with extremely low numbers of B cells in normal skin, [2,5] have added layers of complexity to understanding B‐cell functions in normal and inflamed skin. Targeted B‐cell therapeutics are limited to anti‐CD20 monoclonal antibodies (Rituximab, Ofatumumab, Veltuzumab, Obinutuzumab), with newer therapies including Bruton tyrosine kinase (BTK) inhibitors, BAFF and APRIL inhibitors (Belimumab and Atacicept) and anti‐CD19 monoclonal antibodies (Inebilizumab) [8] .…”