The germinal center of the immune system plays a complicated dual role in the body: vitally selecting B cells secreting high-affinity antibodies to serve the immune system in the fight against foreign invaders, and being the origin of most B cell lymphomas (Nature
From the Max Delbruck Center for Molecular Medicine (MDC) in Berlin, Klaus Rajewsky, PhD, and his team are looking into how various transcription factors and signaling pathways of the germinal center are taken over and manipulated during tumor growth and development.
The germinal center contains reactions between a 'light zone' and a 'dark zone.' The dark zone generates B cells, and the light zone chooses the best candidates to mount an efficient immune response when a pathogen is detected in the body. Rajewsky's group investigated the role of transcription factor "forkhead box O1" (FOXO1), whose specific function has not yet been determined, in dark zone formation and looked for a potential connection to B cells of the germinal center (NIH
The scientists used genetically modified mice to pinpoint the precise link between FOXO1 activity, germinal center B cells, and cancer cell formation. How can these interactions be manipulating cancer formation, they asked. Their findings, published in Immunity
, showed that FOXO1 is necessary for an efficient immune response to pathogens, and the error leading to cancer development remains somewhere between FOXO1 and lymphomagenesis.
Most B cell lymphomas arise from germinal B cells. Even more, FOXO1 mutations have been found to be activated in lymphoma patients.The team from MDC has yet to explain the specific connection between FOXO1 and cancer growth, but the relationship is clearly there.
Watch the following video from the Lymphoma Research Foundation to learn more about a specific type of B cell lymphoma.
Source: MDC in the Helmholtz Association