Pax5 Guards Your Immune System Against Diseases

Immune health can be maintained by the highly compacted ordering and packaging of the genetic material (deoxyribonucleic acid or DNA) in immune cells by a protein called Pax5, new research suggests. The study has just been published in the journal Nature Immunology. Scientists at the Walter and Eliza Hall Institute, Victoria, Australia, have shown that a protein called Pax5 (Paired Box-5) can package DNA in a highly ordered and tightly bound fashion within the nucleus of immune cells such as B-cells. This class of immune cells originate in the bone marrow, hence giving rise to the name, B-cells. These B-cells require the information encoded by the DNA for maintaining their normal structure, function and ability to fight off diseases. If, however, Pax5 malfunctions, it can lead to diseases like cancer, the study findings indicate.

The Walter and Eliza Institute research team was headed by Drs. Rhys Allan and Tim Johanson, in collaboration with Prof. Stephen Nutt, and bioinformatics experts Prof. Gordon Smyth and Dr. Hannah Coughlan.

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Pax5 Keeps DNA Ordered

The study has shown for the first time, how Pax5 can scan the genome, appropriately fold the DNA molecules, and neatly package them into the cell nucleus. In this regard, Johanson indicated that this highly efficient folding and packaging is crucial since, a single cell contains approximately two meters of DNA, which has to fit into a space much lesser than a grain of sand.

He further indicated that cells need to regularly access the information contained in specific regions of the DNA, as and when needed, so that multiple functions can be carried out for maintaining good immune health. For example, DNA contained in B-cells possesses information that is used for producing antibodies, which are the active components of vaccines, which prevent infectious diseases.

Dr. Johanson said: “Think of how a meticulously ordered suitcase increases your chance of finding a specific item of clothing at a moment’s notice, and, how a jumbled case could work against you finding what you need. In the case of our bodies, the difference between order and disorder can be a matter of life and death.”

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Disordered DNA can Cause Disease

Dr. Allan indicated that disordered DNA can lead to complications at a later stage in the process of retrieving information encoded by the DNA molecule. He was of the opinion that even very minute errors during DNA organization could lead to diseases.

Dr. Allan said: “A lack of instructions required to function can put cells at risk of morphing or devolving into something they perhaps shouldn’t be - like a cancer cell. It is therefore unsurprising that Pax5 is faulty in many childhood leukemias.”

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Advances in Bioinformatics

Dr. Hannah Coughlan indicated that the activity of Pax5 across the genome could be visualized for the very first time due to major advances in computing technology. She said: “With the help of powerful computers, we performed thousands of complex calculations to spot the difference in DNA organization when Pax5 was present, versus absent, from the B-cells. Our analyses showed that without Pax5, the cells could no longer package their DNA adequately.” She added: “Bioinformatics is shining a light on how vital factors regulate our DNA. This in turn progresses an understanding of what could be going wrong in cases of disease.”

Dual Function of Pax5

Pax5 has been classically regarded as a transcription factor, which helps to decode the information contained in DNA. However, this is the first time that Pax5 has been assigned a dual function. This second function is its ability to meticulously organize and package DNA molecules, which was not known, until now.

Source of Funding

The research study was funded by grants from the Australian National Health and Medical Research Council (NHMRC), the Australian Research Council, the Victorian State Government and the Australian Government’s NHMRC Independent Research Institute Infrastructure Support Scheme.

Reference:

1. Immune health maintained by meticulously ordered DNA - (https://www.wehi.edu.au/news/immune-health-maintained-meticulously-ordered-dna)

Source-Medindia