Navigation Links
Bcl6 gene sculpts helper T cell to boost antibody production
Date:7/23/2009

HOUSTON - Expression of a single gene programs an immune system helper T cell that fuels rapid growth and diversification of antibodies in a cellular structure implicated in autoimmune diseases and development of B cell lymphoma, scientists at The University of Texas M. D. Anderson Cancer Center reported today in Science Express, the advance online publication of the journal Science.

The gene is Bcl6, which the team found plays the crucial role in differentiating a nave T cell into a T follicular helper cell (Tfh).

"Tfh cells were first noticed in structures called germinal centers found in the lymphoid system - in lymph nodes and the spleen," said senior author Chen Dong, Ph.D., professor in M. D. Anderson's Department of Immunology. Germinal centers are powerful machines that churn out lots of antibodies.

In the adaptive immune system, B cells present an antigen - a distinctive piece of an invading bacterium or virus - to T cells. The bound antigen converts a nave T cell to a helper T cell that secretes cytokines which help the B cells expand and produce a large volume of antibodies to destroy an intruder.

Tfh cells are concentrated with B cells in germinal centers, where they play a helper T cell's traditional role in B cell proliferation and antibody development.

"In germinal centers, the B cells not only proliferate but they also undergo hypermutation in their immunoglobulin genes so they can produce a diverse class of antibodies," Dong said. "These mutations also allow production of antibodies with stronger affinity for their target antigens."

There are pitfalls to this process. Tfh cells and germinal centers have been implicated in antibody-mediated autoimmune diseases such as lupus and rheumatoid arthritis, Dong noted. In these diseases, the germinal centers are likely producing the wrong type of antibody at great volume.

Genetic hypermutation among B cells in germinal centers creates a hotbed of genomic instability, which gives rise to some types of B cell lymphoma, Dong said.

The scientists set out to understand the role of Bcl6, which is short for B-cell lymphoma 6, a transcription factor previously shown to be selectively expressed in Tfh cells.

Last year, Dong and his colleagues reported in the journal Immunity that cytokines IL-6 and IL-21 drive the differentiation of Tfh cells. However, how these cytokines work had been unclear. In the current study, the team reported that that IL-6 and IL-21 induce expression of Bcl6 in the absence of transforming growth factor beta (TGF) to drive T cell differentiation into Tfh. "Not only is Bcl6 a transcription factor expressed by Tfh cells, it also has a major function in generating these cells," Dong said.

When TGF is present with IL-6 and IL-21, T cells differentiate into pro-inflammatory Th17 helper cells.

Another set of experiments showed that Bcl6 expression inhibits a T cell from differentiating into Th17, Th1 or Th2 cells, three other lines of helper cell

Finally, when the Bcl6 gene was knocked out in a mouse model, Tfh was nowhere to be found. "Bcl6 is absolutely required for Tfh generation and it's also important because it blocks other pathways that would lead the T cell into other helper cell types," Dong said.

Solving the molecular programming of Tfh establishes it as the fifth distinct lineage of helper T cell.

Dong and colleagues will continue to characterize Tfh and its relationship to other T helper cells. Dong is co-discoverer of the Th17 cell, which he and colleagues identified as the third T helper cell lineage when conventional wisdom held that there were only two such lines. They also showed that Th17 secretes interleukin-17, which is implicated in both inflammatory and autoimmune diseases.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. Nations Leading Dialysis Provider - DaVita - Partners with eDiets(R) to Launch One-of-a-Kind Diet Helper Online Nutrition and Meal Planning Tool for Late-Stage Kidney Disease Patients and Caregivers
2. Natures helpers: Using microorganisms to remove TCE from water
3. Nightingale announces US$12.3 million sale of its Therapist Helper business
4. Ceridian LifeWorks Offers CareGiverHelper Service to Clients to Ease Stress of Family Caregiving
5. Home Helpers and Veterans Express Helping Spread the Word About Little-Known Veteran's Aid and Attendance Benefit
6. Netsmart Technologies Releases Version 7.5 of Helper(TM) Practice Management Software
7. Netsmart Technologies Releases Version 7.5 Of Helper™ Practice Management Software
8. New treatment boosts muscle function in myasthenia gravis
9. Heavy Drinking Boosts Stroke Risk for Chinese Men
10. Longer ambulance journeys boost death risk for seriously ill patients
11. Traffic Fumes Plus Genes Boosts Kids Asthma Risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... (PRWEB) , ... April 30, 2016 , ... Mercy College ... campus. The following programs will be expanding due to high demand: Master of ... The expansion will begin this summer. , School of Business Graduate Program ...
(Date:4/29/2016)... ... 29, 2016 , ... Our bodies are bombarded daily by environmental and lifestyle ... these stressors is to adopt a more healthful diet, but too many people think ... certified Holistic Nutritionist and the creator of the Newport Beach Cleanse and 14-Day Eating ...
(Date:4/29/2016)... ... 29, 2016 , ... Conditions were ideal for Global Lyme Alliance’s (GLA) 2nd ... sunny skies, a light breeze and temperatures in the 60s. Over 400 runners, walkers ... and Walk and 1-mile walk were held to increase awareness about Lyme disease ...
(Date:4/29/2016)... Kansas City, Missouri (PRWEB) , ... April 29, 2016 , ... ... Unlike traditional crutches which put pressure on the armpits, the M+D Crutch evenly distributes ... less strain on their wrists and hands when using the crutches than with other ...
(Date:4/29/2016)... ... ... City based oral and maxillofacial surgeon Dr. Majid Jamali is an expert in ... apnea. Dr. Jamali is proud to offer this permanent solution to patients who suffer from ... bones. This surgery is performed to correct the alignment of the jaw. It is beneficial ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... -- Automation is one of the best ... growing demands for productivity in speed, accuracy, throughput and ... already adept of a wide range of functions that ... Instrumentation continues to evolve, and is poised to tackle ... years ago. Originally used mostly by the big pharmaceutical ...
(Date:4/28/2016)... April 28, 2016  While Abbott,s announced purchase ... company,s valve repair and stent business, healthcare research ... Abbott more firmly into patient monitoring.  Kalorama said ... growing device areas, with double-digit growth expected the ... Advanced Remote Patient Monitoring . Abbott ...
(Date:4/28/2016)...  Marking its one year anniversary since launching ... risk test, Color Genomics announced a ... impact the most common hereditary cancers affecting both ... analyzes hereditary cancer risks for breast, colorectal, melanoma, ... Color Test is physician ordered and includes genetic ...
Breaking Medicine Technology: