Abstract

The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG) and immunoglobulin A (IgA), previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity.

Highlights

  • Immunoglobulin (Ig), known as antibody, is thought to be produced exclusively by B lineage cells but no other cell types

  • Our study shows that normal skin epidermal cells stain significantly for immunoglobulin G (IgG) and immunoglobulin A (IgA)

  • The abundance of both IgG and IgA in the epidermis is verified by Western blot analysis and, importantly, we find evidence that the rearranged Igγ (IgG heavy chain) and Igα (IgA heavy chain) chains are transcribed in the epidermis

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Summary

Introduction

Immunoglobulin (Ig), known as antibody, is thought to be produced exclusively by B lineage cells but no other cell types. Over the past 10 years, there is growing evidence that many normal or malignant non-B lineage cells, including certain gland epithelial cells [2,3,4,5,6,7], germ cells [8], endothelial cells [9], cardiomyocytes [10], or neurons [11,12], can express Ig, including IgM, IgG [13,14] and IgA [3,15,16,17]. IgG and IgA deposits were frequently observed in epidermal cells and the epidermal stratum basale in several autoimmune diseases [27,28,29] and, occasionally, in normal skin [26,30]

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