3D rendering of a B cell. Photo credit: Blausen.com employees (2014). “Medical Gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI: 10.15347 / wjm / 2014.010. ISSN 2002-4436. CC BY-SA 4.0
B cells are the immune cells responsible for making antibodies, and most B cells, known as B2 cells, produce antibodies in response to a pathogen or vaccine and provide defense and immunity to infection. However, a small subset of long-lived B cells known as B1 cells is vastly different from their short-lived cousins, the B2 cells. Instead of producing antibodies in response to intruders, they spontaneously produce antibodies that perform important household functions, e.g. B. Removing wastes such as oxidized LDL cholesterol from the blood.
Like all cells in the body, B1 and B2 cells have the same DNA and therefore the same set of starting commands. Through epigenetic modifications that open and close different areas of the genome to the machinery that reads the genetic instructions, the same genome can be used to create unique instructions for each cell type. Understanding how the various epigenetic landscapes – the changes in instructions – account for these differences in such similar cells is both an important fundamental question in immunology and can help scientists better identify diseases related to B-cell dysregulation to understand.
Shiv Pillai, MD, Ph.D., a core member of the Ragon Institute of MGH, MIT, and Harvard, studied the DNA modifications present in both cell types at different stages of development to identify an epigenetic signature that can determine whether a cell will become a B1 or a B2 cell. This work was recently published in the journal Nature Communications.
“Through our analysis, we found that the fate of a B cell is determined by epigenetic modifications controlled by a protein called DNMT3A,” says Dr. Vinay Mahajan, professor of pathology at the Ragon Institute and lead author of the paper. “Human genetic studies link the genomic regions with these markers to a variety of immune-mediated disorders.”
The team studied CpG methylation, a type of epigenetic modification that opens up specific areas of DNA and marks regulatory elements that can turn genes on or off. They discovered a number of regulatory elements with unique characteristics in these B1 and B2 cells. In most cases, CpG methylation is permanent and after addition is even passed on when the cell is replicating. In B cells, the DNMT3A protein had to work continuously to maintain these epigenetic modifications. If DNMT3A were removed from B1 cells, the epigenetic modifications would be lost and chronic lymphocytic leukemia (CLL), a cancer caused by the uncontrolled replication of B1 cells, would occur.
“These unique B1 cells are critical to our ability to stay healthy,” says Pillai. “The antibodies they make help prevent blood clots and heart attacks. If we understand what genetic factors regulate them at the same time, we can better understand what happens when their regulation goes wrong and leads to CLL and other diseases.”
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Vinay S. Mahajan et al., B1a and B2 cells are characterized by different CpG modification states in DNMT3A-maintained enhancers, Nature Communications (2021). DOI: 10.1038 / s41467-021-22458-9 Provided by Massachusetts General Hospital
Quote: Epigenetic changes determine the fate of a B-cell (2021, May 13), which was accessed on May 14, 2021 from https://medicalxpress.com/news/2021-05-epigenetic-fate-cell.html
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