B-Cell DNA Repair Flaw Linked to Lymphoma Risk
Author: University of Sheffield
Published: 2011/06/09 - Updated: 2025/11/10
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Treatment of Cancer - Academic Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research from the University of Sheffield's Institute for Cancer Studies represents a significant advancement in understanding B-cell lymphoma, one of the UK's most common cancers affecting both adults and children. The peer-reviewed findings, funded by Leukemia and Lymphoma Research, BBSRC, and Yorkshire Cancer Research, challenge the prevailing theory about lymphoma's origins by identifying a previously unknown mechanism: B-cells fail to repair the majority of their DNA and only maintain genes they're actively using, which becomes problematic when the cells proliferate in response to infection and replicate damaged DNA, leading to cancer-causing mutations.
Led by Dr. Thierry Nouspikel, the team's discovery is particularly relevant because it explains why UV exposure stands as the primary environmental risk factor for lymphoma, while also accounting for increased risks from air pollution and smoking - information that proves invaluable for prevention strategies accessible to everyone, including older adults and people with compromised immune systems who face elevated cancer risks and would benefit most from understanding modifiable environmental factors they can control - Disabled World (DW).
Introduction
Researchers from the University of Sheffield have discovered valuable insight into how people develop B-cell lymphoma, one of the most common cancers in the UK. The team, from the University's Institute for Cancer Studies and funded by Leukemia and Lymphoma Research, Biotechnology and Biological Sciences Research Council (BBSRC) and Yorkshire Cancer Research, found that a mechanism different to that previously thought to be the cause of lymphoma may be responsible for the development of the disease.
Main Content
Lymphoma is a type of cancer that affects the blood, originating in the lymph glands.
B-cells are the immune cells in the human body that are responsible for producing antibodies to fight infections and provide long-term immunity. B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin's lymphomas.
Prior to this research, the main theory to explain the origins of lymphoma was the malfunction of a mechanism (somatic hyper-mutation) used by B-cells to modify the genes coding for antibodies. This mechanism is required to produce highly specific antibodies, but it also accidentally alters other genes, leading to lymphoma.
However, the team from the University knew that this theory only accounted for affecting a handful of genes, and the model could only explain certain types of lymphoma.
Led by Dr Thierry Nouspikel, the researchers discovered another mechanism, which potentially affects many more genes and can account for a wider palette of lymphomas. The research found that B-cells actually do not repair the bulk of their DNA and only take care of the few genes they are using. When the B-cells are inert in the blood flow, this is not a problem. However, when they receive a stimulation (e.g. an infection) they start to proliferate and then produce antibodies.
To proliferate they must replicate their DNA, and replication of damaged DNA results in the introduction of mutations, the accumulation of which can lead to lymphoma. Dr Nouspikel's team have designed a novel method to specifically detect such mutations, and have proved that they do occur in genes that have been implicated in lymphoma.
The researchers demonstrated that B-cells are deficient in one of the main DNA repair pathways, known as Nucleotide Excision Repair. This pathway repairs a lot of different DNA lesions, including UV-induced damage and chemical adducts (e.g. from air pollution and cigarette smoke). Their model therefore explains why strong UV exposure (e.g. unprotected sun bathing) is the number one environmental risk factor for lymphoma and also supports the evidence that exposure to air pollution and smoking are also risk factors.
Dr Nouspikel said:
"Lymphoma is one of the ten most frequent cancers in adults in the UK, and the third among children. If we want to come up with efficient strategies for prevention and therapy, it is crucial to understand what causes it. The novel mechanism we have discovered potentially accounts for the development of many different types of lymphoma. It may also explain why strong exposure to sunlight is the main environmental risk factor for this cancer."
Insights, Analysis, and Developments
Editorial Note: What makes this discovery particularly compelling is how it reframes our understanding of cancer prevention as something within reach of everyday choices. By establishing the direct link between environmental exposures and a fundamental cellular repair deficiency, the Sheffield team has given people concrete reasons to limit sun exposure, avoid smoking, and minimize air pollution contact—not through vague health warnings, but through hard science showing exactly how these factors exploit a specific vulnerability in our immune cells. For anyone navigating health challenges or simply trying to reduce cancer risk, this kind of mechanistic clarity transforms prevention from abstract advice into actionable strategy - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by University of Sheffield and published on 2011/06/09, this content may have been edited for style, clarity, or brevity.