New role discovered for a well-known gene in the survival of white blood cells

May 31, 2017

Researchers have clarified the role of a gene critical for the development of a type of white blood cells, known as B cells, which produce antibodies and serve as a "memory" for the immune system. This finding may open up a new therapeutic avenue for leukemia and autoimmune diseases.

Led by Kong-Peng Lam of the Bioprocessing Technology Institute at A*STAR, the research team used mutated mice to investigate the role of c-Abl, a proto-oncogene which is involved in molecular signaling in a wide range of tissues and has been implicated in leukemia. Earlier studies had shown that c-Abl is essential early in the
development of B cells, but its role later in B cell development was unclear.

The team engineered a mouse in which c-Abl is conditionally knocked out after the early stages of B cell development, allowing immature B cells to form normally. By disrupting the gene only when a B cell became activated by binding an antigen, the researchers were able to decouple the gene's role in the early and late stages of B cell differentiation.

As they mature, B cells develop into several subtypes. While two types of B cells, germinal center and memory B cells, were unaffected by the loss of c-Abl, the team measured lower levels of plasma B cells in the mutated mice, as well as a decrease in specific antibodies.

By growing cultures of immature B cells and stimulating them to mature, the team discovered that the mutated cells could develop into antibody-producing plasma cells, but the cells didn't survive. In the absence of c-Abl, the mutant plasma cells are eliminated via a process of controlled cell death known as apoptosis. When the team also knocked out the apoptosis-related gene BIM, the mutant mice had a normal plasma cell count.

As c-Abl is known to regulate STAT3, a gene which promotes plasma cell survival, the researchers suspected that STAT3 may be involved in the death of the mutated cells. Measurements revealed reduced STAT3 activity in the mutant mice. In addition, the number of plasma cells returned to normal when the team treated with Colivelin, which activates STAT3, confirming that plasma cell death occurs via defective STAT3 signaling in the c-Abl mutants.

These findings may shed light on the development and treatment of multiple myeloma, a cancer of , as well as the treatment of . "Targeting c-Abl could eliminate that produce autoantibodies that destroy healthy tissues," says Lam.

Explore further: Premature cell differentiation leads to disorders in pancreatic development

More information: Yan-Feng Li et al. Tyrosine kinase c-Abl regulates the survival of plasma cells, Scientific Reports (2017). DOI: 10.1038/srep40133

Related Stories

Premature cell differentiation leads to disorders in pancreatic development

April 11, 2017
Researchers at the University of Helsinki, Finland, have uncovered a mechanism through which a mutation in the STAT3 gene leads to a disorder in the development of the pancreas and to infant diabetes.

Shp1 protein helps immune system develop its long-term memory

March 18, 2015
A protein called Shp1 is vital to the immune system's ability to remember infections and fight them off when they reappear, researchers at A*STAR have found.

Lamprey-derived antibody specifically recognizes human plasma cells

March 17, 2016
Antibody-secreting plasma cells arise from B cell precursors and are essential for adaptive immune responses against invading pathogens. Plasma cell dysfunction is associated with autoimmune and neoplastic disorders, including ...

Learning how a key protein affects programmed cell death could help to develop vaccines and drugs

April 30, 2015
A*STAR researchers have clarified the role of one particular regulatory protein in controlling the development of plasma cells, opening up several new avenues toward clinical applications.

The function of mature B cells is regulated by a small genomic cluster called mir-17-92

February 11, 2016
B cells are immune cells that generate antibodies against foreign antigens and play an important role in fighting pathogens. The overproduction of antibodies is a cause of the autoimmune disease lupus, leading to kidney dysfunction. ...

Genetic control of immune cell proliferation

April 19, 2017
Germinal centers are transient structures in the lymph nodes where antibody-producing B cells proliferate and differentiate at extraordinary rates. Germinal centers can be visually divided into a dark zone and light zone. ...

Recommended for you

Study shows stress could be just as unhealthy as junk food

October 16, 2017
We all know that a poor diet is unhealthy, but a new BYU study finds that stress may just as harmful to our bodies as a really bad diet.

Childhood poverty, poor support may drive up pregnant woman's biological age

October 16, 2017
Pregnant women who had low socioeconomic status during childhood and who have poor family social support appear to prematurely age on a cellular level, potentially raising the risk for complications, a new study has found.

Blood vessel 'master gene' discovery could lead to treatments for liver disease

October 16, 2017
Scientists have identified a key gene in blood vessels which could provide a new way to assess and potentially treat liver disease.

Chronic inflammation plays critical role in sustained delivery of new muscular dystrophy therapy

October 16, 2017
Macrophages, a type of white blood cell involved in inflammation, readily take up a newly approved medication for Duchenne muscular dystrophy (DMD) and promote its sustained delivery to regenerating muscle fibers long after ...

New study demonstrates importance of studying sleep and eating in tandem

October 13, 2017
A new study from scientists on the Florida campus of The Scripps Research Institute (TSRI) offers important insights into possible links between sleep and hunger—and the benefits of studying the two in tandem. A related ...

'Ridiculously healthy' elderly have the same gut microbiome as healthy 30 year-olds

October 11, 2017
In one of the largest microbiota studies conducted in humans, researchers at Western University, Lawson Health Research Institute and Tianyi Health Science Institute in Zhenjiang, Jiangsu, China have shown a potential link ...

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.