Epigenetic changes influence the fate of B cells

3D rendering of B cells. Credits: staff (2014). “Blausen Medical 2014 Medical Gallery”. 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 involved in the production of antibodies, and most B cells, known as B2 cells, produce antibodies in response to pathogens or vaccines, providing protection and immunity against infection. However, a small subset of long-lived B cells, known as B1 cells, are quite different from their short-lived cousin B2 cells. Instead of producing antibodies in response to intruders, it spontaneously produces antibodies that perform important housekeeping functions such as removing waste products such as oxidized LDL cholesterol from the blood.

Like all cells in the body, B1 and B2 cells have the same DNA and therefore have the same set of initiation instructions. The same genome can be used to create instructions specific to each cell type through epigenetic changes that open and close different regions of the genome to the mechanisms that read genetic instructions. Understanding how different epigenetic landscapes (changes in instruction) enable these differences in such similar cells is an important basic question in immunology, and scientists ask. It helps to better understand the diseases associated with B cell dysregulation.

Shiv Pillai, MD, Ph.D., core members of the Ragon Institute of MGH, MIT, and Harvard. Study DNA modifications that are present in both cell types at various stages of development, and the cells are B1 or B2 cells.This work was recently published in the journal Nature Communications..

“Our analysis shows that the fate of B cells is determined by an epigenetic modification driven by a protein called DNMT3A,” said Vinay Mahajan, a pathology instructor and lead author of the paper at the Ragon Institute. MD, Ph.D. Says. “Genetic studies in humans have linked genomic regions with these markers to a variety of immune disorders.”

The team studied CpG methylation, a type of epigenetic modification that opens specific regions of DNA and marks regulatory elements that can turn genes on or off. They discovered a set of regulatory elements with unique functions in these B1 and B2 cells. In most cases, CpG methylation is permanent and once added, it is inherited when the cell replicates. However, in B cells, the protein DNMT3A needed to function continuously to maintain these epigenetic modifications. When DNMT3A is removed from B1 cells, epigenetic modifications are lost, resulting in chronic lymphocytic leukemia (CLL), a cancer caused by uncontrolled replication of B1 cells.

“These unique B1 cells are very important for maintaining good health,” says Pilai. “The antibodies they produce help prevent blood clots and heart attacks. At the same time, understanding which genetic factors regulate them can lead to poor regulation of them, leading to CLL and other illnesses. It helps you better understand what happens when you connect. ”

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For more information:
Vinay S. Mahajan et al, B1a and B2 cells are characterized by different CpG modification status in enhancers maintained by DNMT3A. Nature Communications (2021). DOI: 10.1038 / s41467-021-22458-9

Provided by Massachusetts General Hospital

Quote: Epigenetic changes of B cells (May 13, 2021) obtained from on May 13, 2021 Depends on fate

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Epigenetic changes influence the fate of B cells

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