Faster, higher, stronger: A protein that enables powerful initial immune response

June 9, 2014, The Wistar Institute

Your first response to an infectious agent or antigen ordinarily takes about a week, and is relatively weak. However, if your immune system encounters that antigen a second time, the so-called memory response is rapid, powerful, and very effective.

Now, a team of researchers at The Wistar Institute offers evidence that a protein, called Foxp1, is a key component of these antibody responses. Manipulating this protein's activity, they say, could provide a useful pathway to boosting antibody responses to treat infectious diseases, for example, or suppressing them to treat autoimmune disorders. Their findings appear online in the journal Nature Immunology.

"Foxp1 has an important role in our antibody immune responses, and if we could find a way to regulate Foxp1 activity in a subset of T cells, the CD4+ T cells, it could have some profound impact on the antibody responses," said Hui Hu, Ph.D., senior author of the study and associate professor at Wistar's National Cancer Institute-designated Cancer Center.

"Repressing Foxp1 activity, for example, we may be able to make antibody responses faster-acting and more effective, which could be crucial in, say, a pandemic when time is a critical factor," Hu said. "Alternatively, if we could enhance the effectiveness of this protein, we may be able to significantly dampen the that are unwanted in some cases of autoimmune diseases such as lupus."

Previously, the Hu laboratory determined that Foxp1 was responsible for keeping T cells—the that mediate our —on "active stand-by mode," a process called quiescence. In the present study, Hu teamed with the laboratories of Louise C. Showe, Ph.D., professor in the Wistar Cancer Center's Molecular and Cellular Oncogenesis program, which provided crucial genomics expertise, and Jan Erickson, Ph.D., professor in the Tumor Microenvironment and Metastasis program, which offered expertise in the study of autoimmunity and the activation of B cells, the cells that generate antibodies.

According to their Nature Immunology report, variants (or isoforms) of Foxp1 (called Foxp1A and Foxp1D) are critical regulators for the formation of a type of T cells, called T Follicular Helper (TFH) cells. These TFH cells then go on to enable B cells in creating long-lived, highly reactive antibodies. The proteins are transcription factors, meaning they work by binding to DNA to control which genes in these T cells are "read" or translated into protein.

In the initial days of an immune response, the Foxp1 proteins determine how TFH cells arise from activated T . "The two isoforms act as regulators of TFH differentiation in the early moments of the , where they effectively act as gatekeepers to slow TFH development, " Hu said. "They constitute a 'double-check' system that prevents the humoral branch of the immune system from acting too hastily."

Explore further: Direct proof of how T cells stay in 'standby' mode

Related Stories

Direct proof of how T cells stay in 'standby' mode

May 5, 2011
the white blood cells that act as the police of the immune system—are in what immunologists call a "quiescent state," a sort of standby mode. For years, scientists have wondered if quiescence occurred by default or whether ...

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 ...

Scientists uncover features of antibody-producing cells in people infected with HIV

June 3, 2014
By analyzing the blood of almost 100 treated and untreated HIV-infected volunteers, a team of scientists has identified previously unknown characteristics of B cells in the context of HIV infection. B cells are the immune ...

Specialized regulatory T cell stifles antibody production centers

July 25, 2011
A regulatory T cell that expresses three specific genes shuts down the mass production of antibodies launched by the immune system to attack invaders, a team led by scientists at The University of Texas MD Anderson Cancer ...

New understanding of tiny RNA molecules could have far-ranging medical applications

June 30, 2013
A team led by scientists at The Scripps Research Institute (TSRI) has identified a family of tiny RNA molecules that work as powerful regulators of the immune response in mammals. Mice who lack these RNA molecules lose their ...

Recommended for you

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, ...

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.

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 ...

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.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

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.