title: Spontaneous production of immunoglobulin M in human epithelial cancer cells.
abstract: It is well known that B-1 B cells are the main cell type that is responsible for the production of natural immunoglobulin M (IgM) and can respond to infection by increasing IgM secretion. However, we unexpectedly found that some epithelial cells also can express rearranged IgM transcript that has natural IgM characteristics, such as germline-encoded and restricted rearrangement patterns. Here we studied IgM expression in human non-B cells and found that IgM was frequently expressed by many human epithelial cancer cells as well as non-cancer epithelial cells. Moreover, CD79A and CD79B, two molecules that are physically linked to membranous IgM on the surface of B cells to form the B cell antigen receptor complex, were also expressed on the cell surface of epithelial cancer cells and co-located with IgM. Like the natural IgM, the epithelial cancer cell-derived IgM recognized a series of microbial antigens, such as single-stranded DNA, double-stranded DNA, lipopolysaccharide, and the HEp-2 cell antigen. More important, stimulation of the toll-like receptor 9 (TLR9), which mimics bacterial infection, substantially increased the secretion of IgM in human epithelial cancer cells. These findings indicate that human epithelial cancer cells as well as non-cancer epithelial cells can spontaneously produce IgM with natural antibody activity.
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Wenwei
authors.initials: W
authors.lastname: Shao
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Liao
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Geng
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000912:Antibodies, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007150:Immunohistochemistry; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D046888:Tissue Array Analysis; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D000912:Antibodies, Neoplasm; D001324:Autoantigens; C408982:CPG-oligonucleotide; D007075:Immunoglobulin M; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D011947:Receptors, Antigen, B-Cell; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D002738:Chloroquine