Investigating immune responses

A molecule produced by hepatitis B virus prompts the body’s immune cells to leap into action.

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A small signalling protein produced by one type of immune cell activates and promotes the proliferation of another. This B-cell activating factor (BAFF) appears to play an important role in combating hepatitis B infection. Understanding how the body’s immune cells respond to hepatitis B virus (HBV) could lead to ways to combat it.

Hepatitis B virus (HBV) is transmitted through contact with blood or bodily fluids of an infected person. It attacks the liver and can lead to cirrhosis and cancer. An estimated 257 million people have HBV infection. A vaccine that is 95% effective has been available since 1982. Although treatments aren’t available for the acute form of the disease, drugs can slow the progression of cirrhosis and reduce the incidence of liver cancer.

The roles of two types of immune cells, monocytes and B-lymphocytes, in HBV infections are still not clear, says Yulian Jiao from Shandong University in Jinan, China. “We are very interested in the interaction between these immune cells and HBV; more specifically how a viral protein, the HBV e antigen or HBe, affects these two cell types. HBe is a known marker for HBV replication and is also reported to be a key immune regulator, particularly during chronic HBV infection.”

Jiao and his team conducted a unique series of experiments using a lentivirus (a ‘carrier’ virus harbouring the HBe gene) to express HBe in culture plates containing monocytes and B-lymphocytes. This allowed them to mimic the processes HBe triggers in the body during HBV infection.

They found that HBe severely inhibited the monocytes’ ability to move quickly, which is needed at times of infection. They also discovered that HBe prompts monocytes to increase their production of pro-inflammatory proteins and to accelerate the expression of a factor, called BAFF, that activates B-lymphocytes and promotes their proliferation. BAFF levels in HBe-positive patient blood samples tend to be far higher than in HBe-negative patients. Jiao’s team also found that HBe directly triggered B lymphocyte activation.

“As BAFF increases, the activation and proliferation of B-lymphocytes increases. In fact, it appears the B cells become ‘supercharged’ and in turn trigger strong and appropriate immune responses,” says Jiao. “In addition, the antibodies produced by B lymphocytes neutralize the virus, helping to clear infection.”

References

  1. Lu, B., Zhang, B., Wang, L., Ma, C., Liu, X. et al . Hepatitis B virus e antigen regulates monocyte function and promotes B lymphocyte activation. Viral Immunology30 (2017). | article

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