IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09

AUTHORS

Louise Saul, Kristina M Ilieva, Heather J Bax, Panagiotis Karagiannis, Isabel Correa, Irene Rodriguez-Hernandez, Debra H Josephs, Isabella Tosi, Isioma U Egbuniwe, Sara Lombardi, Silvia Crescioli, Carl Hobbs, Federica Villanova, Anthony Cheung, Jenny L C Geh, Ciaran Healy, Mark Harries, Victoria Sanz-Moreno, David J Fear, James F Spicer, Katie E Lacy, Frank O Nestle, Sophia N Karagiannis

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. More... »

PAGES

29736

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep29736

    DOI

    http://dx.doi.org/10.1038/srep29736

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1003310898

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27411958


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