Product Citations: 2

Cutaneous lesions in lupus erythematosus (LE) subtypes are heterogenous. In line with the heterogeneity of the clinical presentation, the underlying lesional inflammation in LE skin samples is defined by different immune cell infiltrates. Pathophysiologically, lesional inflammation is driven by autoreactive cytotoxic T cells, targeting keratinocytes; plasmacytoid dendritic cells (pDCs), producing large amounts of interferon (IFN); and B cells, whose function in cutaneous LE is still unclear. This study aims to (a) classify inflammatory patterns with regard to the dominating cell type or cytokine expression and (b) investigating the specific role of B cells in LE skin lesions. Therefore, the immunohistological expression of inflammatory surrogates (CD20, CD123, MXA) in skin samples of n = 119 LE (subtypes: subacute cutaneous LE, chronic discoid LE, chilblain LE, LE tumidus, other LE) and n = 17 patients with inflammatory skin diseases (atopic dermatitis, psoriasis) were assessed. Samples were classified with regard to inflammatory groups. In addition multiplex-immunohistochemical analyses of n = 17 LE skin samples focusing on lesional B cells were conducted. In this study, we show that cutaneous lesions present with eight different inflammatory groups dominated by B cells, pDCs, a strong IFN expression, or overlapping patterns. Altogether, LE subtypes show heterogenous infiltration regardless of LE subtype, certain subtypes display a preference for infiltration groups. Furthermore, lesional B cells either form diffuse infiltrates or pseudofollicular structures, wherein they show antigen-presenting and T cell-activating properties. Altogether, in the light of emerging targeted therapeutic options, we suggest histological assessment in regard to B-cell or pDC preponderance to allow tailored treatment decisions.
Copyright © 2022 de Vos, Guel, Niebel, Bald, ter Steege, Bieber and Wenzel.

  • IHC
  • Homo sapiens (Human)
  • Immunology and Microbiology

Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement.

In The Journal of Immunology on 15 April 2017 by Schuh, E., Musumeci, A., et al.

The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface. After engagement of TLR7/8 or TLR9, BCMA was detected also on the cell surface of pDCs. The display of BCMA on the surface of human pDCs was accompanied by release of soluble BCMA (sBCMA); inhibition of γ-secretase enhanced surface expression of BCMA and reduced the release of sBCMA by pDCs. In contrast with human pDCs, murine pDCs did not express BCMA, not even after TLR9 activation. In this study, we extend the spectrum of BCMA expression to human pDCs. sBCMA derived from pDCs might determine local availability of its high-affinity ligand APRIL, because sBCMA has been shown to function as an APRIL-specific decoy. Further, therapeutic trials targeting BCMA in patients with multiple myeloma should consider possible effects on pDCs.
Copyright © 2017 by The American Association of Immunologists, Inc.

  • Immunology and Microbiology
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