Nav: Home

Research helps explain how B cell metabolism is controlled

January 23, 2017

La Jolla, Calif., January 23, 2016 (embargoed until 11:00 A.M. EST) -- B cells, the lymphocytes best known for making antibodies, live a complex life. They start developing in the bone marrow and then move through the spleen, lymph nodes and blood, taking on tasks that range from recognizing foreign substances to replication, quiescence, and generating a lasting memory of pathogens. But little is known about how B cell metabolism adapts to each of these environments, insights that may improve our understanding of B cell diseases, such as non-Hodgkin's lymphoma.

"Our research shows that the protein GSK3 plays a crucial role in helping B cells meet the energy needs of their distinct states," says Robert Rickert, Ph.D., director of the Tumor Microenvironment and Cancer Immunology Program at Sanford Burnham Prebys Medical Discovery Institute (SBP). "It acts as a metabolic sensor, or checkpoint, that promotes the survival of circulating B cells while limiting growth and proliferation of B cells in germinal centers. The findings are particularly relevant for certain B cell pathologies, including lymphoma subtypes, where there is an increased demand for energy to support the hyperproliferation of cells in a microenvironment that may be limited in nutrients."

B cells have different metabolic needs depending on their environment. In the blood, circulating B cells are quiescent, consuming little energy. In germinal centers--the sites within lymph nodes where mature B cells cluster--B cells proliferate and undergo hypermutation of their antibody genes to generate high-affinity antibodies. These processes require enormous amounts of energy, so these B cells consume lots of sugars, fatty acids and amino acids.

The new study, published today in Nature Immunology, found that GSK3 adjusts metabolism to match each of these needs. In circulating B cells, GSK3 limits overall metabolic activity, while in proliferating B cells in germinal centers, GSK3 slows glycolysis and production of mitochondria.

GSK3 function is essential for B cell survival in germinal centers. To understand why, Rickert's team looked at how B cells in these regions generate energy, and found that because these B cells are so metabolically active, they consume nearly all available glucose. That switches on a secondary, less efficient but non-oxygen-dependent means of generating energy called glycolysis. High glycolytic activity leads to accumulation of toxic reactive oxygen species (ROS), as does rapid manufacture of mitochondria, which tend to leak the same chemicals. Thus, by restraining metabolism in specific ways, GSK3 prevents ROS-induced cell death.

"Our results were really surprising," Rickert commented. "Until now, we would have thought that slowing metabolism would only be important for preventing B cells from becoming cancerous--which it indeed may be. These studies provide insight into the dynamic nature of B cell metabolism that literally 'fuels' differentiation in the germinal center to produce an effective antibody response"

"It's not yet clear whether or how GSK3 might be a target for future therapies for B cell-related diseases, but this research opens a lot of doors for further studies," Rickert said. "To start with, we plan to investigate how GSK3 is regulated in lymphoma and how that relates to changes in metabolism. That research could lead to new approaches to treating lymphoma."
-end-
This research was performed in collaboration with scientists at Eli Lilly and the Lunenfeld-Tanenbaum Research Institute at the University of Toronto. Funding was provided by the National Institutes of Health, the Lilly Research Award Program, the Arthritis National Research Foundation, and the Canadian Institutes of Health Research.

About SBP

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children's diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs about 1,100 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford-Burnham Prebys Medical Discovery Institute

Related Lymphoma Articles:

The gene behind follicular lymphoma
EPFL scientists have discovered an important gene whose loss lies behind follicular lymphoma, an incurable cancer.
Hodgkin lymphoma survivors at high risk of second cancers
Patients who are cured of Hodgkin lymphoma are at a high risk of developing a second type of cancer, particularly if they have a family history of the disease, a major new study reports.
Follicular lymphoma: A tale of 2 cancers
Many people survive well beyond 10 years following diagnosis of follicular lymphoma.
Patients with advanced lymphoma in remission after T-cell therapy
In a paper published today in Science Translational Medicine, researchers from Fred Hutchinson Cancer Research Center shared data from an early-phase study of patients with advanced non-Hodgkin lymphoma (NHL) who received JCAR014, a Chimeric Antigen Receptor (CAR) T cell treatment, and chemotherapy.
$2.5 million boost for lymphoma research through Tanoto Foundation
The SingHealth Duke-NUS Academic Medical Centre announced today that a S$2.5 million Tanoto Foundation Professorship in Medical Oncology has been conferred to Assoc Prof Lim Soon Thye, Head and Senior Consultant of the Division of Medical Oncology at the National Cancer Centre Singapore; and Assistant Dean at Duke-NUS Medical School.
Lymphoma overrides a key protein's quadruple locks
Protein chemists at Johns Hopkins report they are closer to explaining why certain blood cancers are able to crack a molecular security system and run rampant.
Study: Bacterium that causes Q fever linked to non-Hodgkin lymphoma
The bacterium that causes Q fever, an infectious disease that humans contract from animals, is associated with an increased risk of lymphoma, according to a study published online today in Blood, the Journal of the American Society of Hematology.
Lymphoma: How the tumor escapes the immune response
Natural killer cells of the immune system can fend off malignant lymphoma cells and thus are considered a promising therapeutic approach.
Follow-up PET/CT more than 95 percent sensitive for non-Hodgkin lymphoma
Non-Hodgkin lymphoma, a potentially devastating cancer of the blood and immune system, can range from relatively easy to treat to very aggressive.
Hodgkin's lymphoma: The treatment can have late sequelae
Hodgkin's lymphoma -- cancer of the lymph nodes -- arises in more than 150 children and adolescents in Germany each year.

Related Lymphoma Reading:

100 Questions & Answers About Lymphoma
by Peter Holman (Author), Gregory Bociek (Author), Jodi Garrett (Author)

Written by oncology experts with over 20 years of experience, 100 Questions and Answers About Lymphoma, Third Edition provides authoritative answers to your questions on lymphoma. Featuring the information you need in one concise, easy-to-read volume, 100 Questions and Answers About Lymphoma, Third Edition is an invaluable resource for newly diagnosed patients, survivors, friends or relatives of either. This newly updated text features information on the latest, cutting-edge treatments and medication, Hodgkin's and Non-Hodgkin's lymphoma, natural killer cells, T-cell lymphoma, autoimmune... View Details


Living with Lymphoma: A Patient's Guide (Johns Hopkins Press Health Books (Paperback))
by Elizabeth M. Adler (Author), Michael R. Bishop (Introduction), W. Jeffrey Baker (Introduction)

When neurobiologist Elizabeth M. Adler was diagnosed with non-Hodgkin lymphoma almost twenty years ago, she learned everything she could about the disease, both to cope with the emotional stress of her diagnosis and to make the best possible decisions for her treatment. In Living with Lymphoma, she combines her scientific expertise and personal knowledge with a desire to help other people who have lymphoma manage this complex and often baffling disease.

With the availability of more effective treatment regimens, many people with lymphoma are living longer; in fact, there are... View Details


Non-Hodgkin Lymphomas
by James O. Armitage MD (Editor), Peter M. Mauch MD (Editor), Nancy Lee Harris MD (Editor), Bertrand Coiffier MD (Editor), Riccardo Dalla-Favera MD (Editor)

Thoroughly updated for its Second Edition, Non-Hodgkin Lymphomas is the definitive textbook on the biology, diagnosis, staging, and treatment of all forms of non-Hodgkin lymphomas. With backgrounds in medical and radiation oncology, molecular biology, and pathology, the editors and contributors provide an international, multidisciplinary approach to the topic.

This edition is the first text using the new World Health Organization classification of non-Hodgkin lymphomas. The book offers complete coverage of the most current techniques for diagnosis, staging, and treatment, the... View Details


Lymphomas and Leukemias: Cancer: Principles & Practice of Oncology, 10th edition
by Vincent T. DeVita Jr. MD (Author), Theodore S. Lawrence MD PhD (Author), Steven A. Rosenberg MD PhD (Author)

Selected from the world’s leading comprehensive cancer textbook, this tightly focused resource provides you with the practical, cutting-edge information you need to provide the best cancer care to each patient.  Lymphomas and Leukemias:  Cancer: Principles & Practice of Oncology, 10th Edition, offers a complete and balanced view of this rapidly changing field, meeting the needs of oncology/hematology practitioners, fellows, and others who need an in-depth understanding of leukemias and lymphomas. The print reference gives you the solid, dependable guidance you have come to expect from... View Details


Lymphoma: Pathology, Diagnosis, and Treatment (Cambridge Medicine (Hardcover))
by Dr Robert Marcus (Editor), John W. Sweetenham (Editor), Michael E. Williams (Editor)

Major advances have occurred in the diagnosis and treatment of lymphoma in recent years. Our understanding of the molecular biology and genetics of the disease has increased exponentially, and significant imaging developments have resulted in earlier and more accurate diagnosis. The new edition of this landmark text places these advances in the context of daily clinical practice. Each chapter has been updated to reflect recent developments, including new treatment agents such as immunomodulatory drugs and the next generation of antibodies, and the increasing prognostic role of PET scanning.... View Details


Johns Hopkins Patients' Guide to Lymphoma
by Aditya Bardia (Author), Eric Seifter (Author)

Johns Hopkins Patients' Guide to Lymphoma is a concise, easy-to-follow "how to" guide that puts you on the path to wellness by explaining lymphoma treatment from start to finish. It guides you through the overwhelming maze of treatment decisions, simplifies the complicated schedule that lies ahead, and performs the task of putting together your plan of care in layman's terms. Empower yourself with accurate, understandable information that will give you the ability to confidently participate in the decision making about your care and treatment. View Details


Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

The revolutionary, New York Times bestselling guide to the powerful lifestyle changes that fight and prevent cancer—an integrative approach based on the latest scientific research
 
“A common-sense blueprint for healthy living.” —Chicago Tribune
 
“Resonating with cancer support communities and recommended nationwide.” —Los Angeles Times
 
“Life affirming . . . filled with practical advice.” —The Seattle Times
 
David Servan-Schreiber was a rising... View Details


Non-Hodgkin's Lymphomas: Making Sense of Diagnosis, Treatment & Options (Patient Centered Guides)
by Lorraine Johnston (Author)

Prior to publication of this resource guide, no book on the market targeted the non-Hodgkin's lymphoma survivor's need for understandable information. While there are medical texts on the non-Hodgkin's lymphomas as well as inspirational first-person accounts from survivors of related cancers such as leukemia, between these two sources of information existed a considerable information gap.

In straightforward language and in a format that anticipates the reader's questions, this book addresses diagnosis and its emotional tumult, finding a good oncologist, the theories and practical... View Details


Recover From Lymphoma: 7 Survivors Tell Their Stories

If you or one of your loved ones has recently been diagnosed with either Hodgkin’s or non-Hodgkin’s lymphoma, the survivor information contained in this book could be the most helpful and uplifting message you have ever read.

Just One Idea In this Book Could Change the Direction of your Healing Journey!
Naturally I hope you will find many ideas to inspire and encourage you as you read the survivors’ stories.

However, even if there is only one idea shared in this book that helps you, it may be the very idea that was needed to change the direction of your... View Details


Skin Lymphoma: The Illustrated Guide
by Lorenzo Cerroni (Author)

Skin Lymphoma: The Illustrated Guide presents a templated, easy to follow approach to the diagnosis of this challenging condition. Hundreds of outstanding full colour images, carefully chosen for their clinical relevance, are complemented by a standard chapter format which covers clinical features, histopathology, diagnosis, treatment and prognosis. Teaching cases throughout the text highlight examples of particular interest for trainees, and summary boxes highlight key points for quick review.

This new fourth edition has been fully updated in line with new WHO... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Inspire To Action
What motivates us to take up a cause, follow a leader, or create change? This hour, TED speakers explore stories of inspirational leadership, and what makes some movements more successful than others. Guests include high school history teacher Diane Wolk-Rogers, writer and behavioral researcher Simon Sinek, 2016 Icelandic presidential candidate Halla Tómasdóttir, professor of leadership Jochen Menges, and writer and activist Naomi Klein.
Now Playing: Science for the People

#474 Appearance Matters
This week we talk about appearance, bodies, and body image. Why does what we look like affect our headspace so much? And how do we even begin to research a topic as personal and subjective as body image? To try and find out, we speak with some of the researchers at the Centre for Appearance Research (CAR) at the University of the West of England in Bristol. Psychology Professor Phillippa Diedrichs walks us through body image research, what we know so far, and how we know what we know. Professor of Appearance and Health Psychology Diana Harcourt talks about visible...