Spontaneous Production of Immunoglobulin M in Human Epithelial Cancer Cells

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.

众所周知，B-1 B细胞是负责产生天然免疫球蛋白M（IgM）的主要细胞类型，并可通过增加IgM分泌来应对感染。然而，我们意外发现部分上皮细胞也可表达具有天然IgM特性的重排IgM转录本，例如胚系编码、限制性重排模式等特征。本研究针对人类非B细胞中的IgM表达情况展开分析，结果发现，多种人类上皮癌细胞与非癌上皮细胞均频繁表达IgM。此外，CD79A与CD79B这两种在B细胞表面与膜型IgM物理结合形成B细胞抗原受体复合物的分子，同样在上皮癌细胞的细胞表面表达，并与IgM共定位。与天然IgM类似，上皮癌细胞来源的IgM可识别一系列微生物抗原，如单链DNA、双链DNA、脂多糖以及HEp-2细胞抗原。更重要的是，模拟细菌感染的Toll样受体9（TLR9）刺激，可显著提升人类上皮癌细胞的IgM分泌水平。上述研究结果表明，人类上皮癌细胞与非癌上皮细胞均可自发性产生具有天然抗体活性的IgM。