title: IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin.
abstract: B cells participate in immune surveillance in human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses in cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B cells in healthy volunteers and melanoma patients (n = 73) and CD22+ cells in melanoma and normal skin samples (n = 189). Normal and malignant skin featured mature IgG and CD22 mRNA, alongside mRNA for the transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses of publically-available data (n = 234 GEO, n = 384 TCGA) confirmed heightened humoral responses (CD20, CD22, AID) in melanoma. Analyses of 51 melanoma-associated and 29 normal skin-derived IgG sequence repertoires revealed lower IgG1/IgGtotal representation compared with antibodies from circulating B cells. Consistent with AID, comparable somatic hypermutation frequencies and class-switching indicated affinity-matured antibodies in normal and malignant skin. A melanoma-associated antibody subset featured shorter complementarity-determining (CDR3) regions relative to those from circulating B cells. Clonal amplification in melanoma-associated antibodies and homology modeling indicated differential potential antigen recognition profiles between normal skin and melanoma sequences, suggesting distinct antibody repertoires. Evidence for IgG-expressing B cells, class switching and antibody maturation in normal and malignant skin and clonally-expanded antibodies in melanoma, support the involvement of mature B cells in cutaneous immunity.
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Saul
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Breast Cancer Now Research Unit, Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, London, United Kingdom.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Ilieva
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Bax
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Correa
authors.affiliation: Tumour Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Rodriguez-Hernandez
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: Debra H
authors.initials: DH
authors.lastname: Josephs
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Isabella
authors.initials: I
authors.lastname: Tosi
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Isioma U
authors.initials: IU
authors.lastname: Egbuniwe
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Skin Tumor Unit, St. John's Institute of Dermatology, Guy's Hospital, King's College London and Guy's and St Thomas' NHS Trust, London, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Lombardi
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Crescioli
authors.affiliation: Wolfson Center for Age-Related Diseases; King's College London, London, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Federica
authors.initials: F
authors.lastname: Villanova
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Breast Cancer Now Research Unit, Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom.
authors.forename: Jenny L C
authors.initials: JL
authors.lastname: Geh
authors.affiliation: Department of Plastic Surgery at Guy's, King's, and St. Thomas' Hospitals, London, United Kingdom.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Healy
authors.affiliation: Clinical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Harries
authors.affiliation: Tumour Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sanz-Moreno
authors.affiliation: Division of Asthma, Allergy and Lung Biology, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Fear
authors.affiliation: Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: James F
authors.initials: JF
authors.lastname: Spicer
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.|Skin Tumor Unit, St. John's Institute of Dermatology, Guy's Hospital, King's College London and Guy's and St Thomas' NHS Trust, London, United Kingdom.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Lacy
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London &NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Karagiannis
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C497867:CD22 protein, human; D007074:Immunoglobulin G; D051918:Sialic Acid Binding Ig-like Lectin 2