Molecular interplay explains many immunodeficiencies

November 11, 2013

Australian scientists have described an exquisitely balanced interplay of four molecules that trigger and govern antibody production in immune cells. As well as being an important basic science discovery, it helps explain why people with mutations in any one of the associated genes cannot fight infection effectively, and develop rare and crippling immunodeficiency disorders.

Our immune system is made of a number of different types of that undertake specific functions. Those that make antibodies are known as 'B cells', and they become active after infection. Once a B cell is activated, it can proliferate into thousands of clones, known as 'plasma cells', which patrol the body and secrete large amounts of antibody to destroy the invader.

Dr Lucinda Berglund and Associate Professor Stuart Tangye, from Sydney's Garvan Institute of Medical Research, are the first to describe a specific molecular process that controls the activation and differentiation of B cells. They used human blood and tissue samples to show that the chemical messaging molecule interleukin 21 (IL-21) activates the STAT3 gene in B cells, which in turn triggers the expression of a molecule known as 'CD25', a that attracts a second messaging molecule, interleukin 2 (IL-2). IL-21 and IL-2 then work co-operatively to induce plasma cell development and . Their findings are published in the international journal Blood.

"The interesting and informative aspect of this finding for me is that some people have mutations in the IL-21 receptor, some have mutations in STAT3, while others have mutations in CD25, and they all have B cell defects," said Associate Professor Tangye.

"By examining B cells from people with specific , we revealed that both components of the IL-21 receptor are critical for B cell function – and people can have mutations in either, with equally debilitating effects. We see these effects in patients with X-linked , whose impaired response to IL-21 causes severe antibody deficiency."

"Patients with mutations in the STAT3 gene develop Hyper IgE Syndrome, another rare immunodeficiency that manifests as compromised antibody production and greatly depleted immune defences."

Immunodeficiencies arising from in single genes give scientists a unique opportunity to understand B cell signaling, and reveal potential targets for modulating B cell responses in immunodeficiency and autoimmunity.

The current study arose from analysing global gene expression in B cells from healthy people and people with STAT3 deficiency – which immediately highlighted genes that were poorly expressed in disease. The Tangye lab plans to investigate other genes that impact the function of B cells.

Explore further: Vaccine blackjack: IL-21 critical to fight against viral infections

More information: bloodjournal.hematologylibrary … 3-06-506865.full.pdf

Related Stories

Vaccine blackjack: IL-21 critical to fight against viral infections

May 23, 2013
(Medical Xpress)—Scientists at Emory Vaccine Center have shown that an immune regulatory molecule called IL-21 is needed for long-lasting antibody responses in mice against viral infections.

Surprise finding reveals how adaptive our immune systems can be

July 15, 2013
(Medical Xpress)—Studies of patients with immunodeficiencies involving single gene mutations can reveal a great deal about our immune systems, especially when actual symptoms do not accord with clinical expectations.

Unsung heroes of antibody production

August 3, 2012
B cells are the body’s antibody factories, standing by to churn out molecules that selectively target foreign threats as a component of the humoral immune response. However, this process also requires T cells to secrete ...

Development of autoimmunity in patients with common variable immune deficiency

September 24, 2013
Common variable immune deficiency (CVID) is a genetic disease associated with enhanced susceptibility to infection, autoimmunity, and decreased antibody production. Mutations in the tumor necrosis factor receptor superfamily ...

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Co-infection with two common gut pathogens worsens malnutrition in mice

July 27, 2017
Two gut pathogens commonly found in malnourished children combine to worsen malnutrition and impair growth in laboratory mice, according to new research published in PLOS Pathogens.

Study sheds light on how body may detect early signs of cancer

July 26, 2017
Fresh insights into how cells detect damage to their DNA - a hallmark of cancer - could help explain how the body keeps disease in check.

How genetically engineered viruses develop into effective vaccines

July 26, 2017
Lentiviral vectors are virus particles that can be used as a vaccine to stimulate the immune system to fight against specific pathogens. The vectors are derived from HIV, rendered non-pathogenic, and then engineered to carry ...

Accounting for human immune diversity increases clinical relevance of fundamental immunological research

July 26, 2017
Mouse models have advanced our understanding of immune function and disease in many ways but they have failed to account for the natural diversity in human immune responses. As a result, insights gained in the lab may be ...

Study suggests same gut bacteria can trigger different immune responses depending on environment

July 24, 2017
(Medical Xpress)—A group of researchers affiliated with several institutions in the U.S. has found that one type of gut bacteria triggers different kinds of immune responses depending on the state of the environment they ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.