Molecular interplay explains many immunodeficiencies

November 11, 2013, Garvan Institute of Medical Research

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

Improving vaccines for the elderly by blocking inflammation

January 22, 2018
By identifying why skin immunity declines in old age, a UCL-led research team has found that an anti-inflammatory pill could help make vaccines more effective for elderly people.

Novel genomic tools provide new insight into human immune system

January 19, 2018
When the body is under attack from pathogens, the immune system marshals a diverse collection of immune cells to work together in a tightly orchestrated process and defend the host against the intruders. For many decades, ...

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

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.