B1 or B2?
Epigenetic changes determine the fate of the B cell
Anna Yudina, "Scientific Russia"
Scientists from the Ragon Institute at Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard have discovered epigenetic changes unique to B cells and their subtypes, according to a press release Epigenetic changes drive the fate of a B cell.
Article by Mahajan et al. B1a and B2 cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers published in the journal Nature Communications – VM.
B cells are immune cells responsible for creating antibodies, and most B cells, known as B2 cells, produce antibodies in response to a pathogen or vaccine, providing protection and immunity against infections. But a small subset of long-lived B cells, known as B1 cells, are very different from their short-lived counterparts, B2 cells. Instead of producing antibodies in response to invaders, they spontaneously produce antibodies that perform vital internal functions, such as removing waste, such as oxidized LDL cholesterol, from the blood.
Like all cells in the body, cells B1 and B2 have the same DNA and, therefore, the same starting set of instructions. It is through epigenetic modifications that open and close different regions of the genome for a mechanism that reads genetic instructions that the same genome can be used to create unique instructions for each type of cell. Understanding how different epigenetic landscapes – changes in instructions – account for these differences in such similar cells is both an important fundamental issue in immunology and can help scientists better understand diseases associated with B-cell dysregulation.
Shiv Pillai, MD, one of the main collaborators of the Ragona Institute, studied the DNA modifications present in both types of cells at different stages of development to identify epigenetic signs that can determine whether a cell becomes a B1 or B2 cell.
"Thanks to our analysis, we found that the fate of the B cell is determined by epigenetic modifications controlled by the DNMT3A protein," says Vinay Mahajan, MD, lecturer in pathology at the Ragona Institute and the first author of the paper. "Genetic studies in humans link sections of the genome with these markers to various immune–mediated disorders."
The team studied CpG methylation, a type of epigenetic modification that unlocks specific regions of DNA and marks regulatory elements that can turn genes on or off. They found a set of regulatory elements with unique features in these B1 and B2 cells. In most cases, CpG methylation is permanent and, when added, is even transmitted during cell replication. But in B cells, the DNMT3A protein must constantly work to maintain these epigenetic modifications. If DNMT3A was removed from B1 cells, epigenetic modifications were lost and chronic lymphoma leukemia (CLL), a cancer caused by uncontrolled replication of B1 cells, occurred.
"These unique B1 cells are vital to our ability to stay healthy," Pillai says. – The antibodies they create help prevent blood clots and heart attack. At the same time, understanding which genetic factors regulate them can help us better understand what happens when their regulation goes wrong, which leads to chronic lymphocytic leukemia and other diseases."
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