B cells and cancer: what are the roles of metabolism and ROS?

Explaining their research in less than 90 seconds: 8 young researchers from Luxembourg took up the challenge in the 2nd edition of the video series "My research in 90 seconds". In this episode, Davide G. Franchina talks about B cell proliferation (cells of the immune system) and how his studies might lead to a better understanding of cancer! More about this in the video - and further details in his article.

The video and the accompanying article were produced as part of a “Science Communication Course” for PhD students at the University of Luxemburg.

Author: Davide G. Franchina (PhD at LIH)
Editor : Michelle Schaltz (FNR)
Video: Jean-Paul Bertemes (FNR) & Moast Creative Studios

B cells are known to produce antibodies. Antibodies are proteins used by the immune system to detect and neutralize pathogens such as pathogenic bacteria and viruses. To produce such antibodies, B cells go through an activation process that includes proliferation. During proliferation the B cell grows and divides and a lot of energy is consumed through metabolic reactions. Together with energy, cellular metabolism produces reactive oxygen species, or ROS. ROS regulate cellular functions and their level is monitored by antioxidants, which determine the quantity of free ROS in the cell. By altering antioxidants it is thus possible to study how ROS interfere with B cell functions.

The ROS-antioxidants balance alters the proliferation of B cells

When activated, B cells need more energy, therefore ROS concentration increase. Antioxidants, of which the most important is glutathione, act as cellular “mop” by blocking ROS. The balance among energy production, ROS and antioxidants is important for the regulation of many cellular functions.

One of the features of cellular activation is growth in size and proliferation. Indeed, B cells get bigger to accommodate the needs for the production of antibodies, and divide to increase antibody production.

Researchers found out that when glutathione is eliminated, B cell proliferation decreases. This effect has to be studied in detail to find out how ROS regulate proliferation. One possibility could be, that regulation is carried out through alteration of protein functions. Investigating this possibility could reveal novel mechanisms to help understand proliferation of cancer cells.

The B cell response and cell proliferation in cancer

The principle of immune activation relies on the recognition of a foreign protein by the immune cells. B cells bind to a foreign protein using Y-shaped proteins called B cell receptors (which have the same structure as antibodies), situated on the B cell’s surface. After binding, the B cell proliferates, creating a group of B cells which will differentiate and secrete antibodies.

In fact, the very first step of the B cell response to a pathogen is proliferation, which is a coordinated or organized process and is crucially linked to the increase in the cell’s energy needs and ROS production.

B cells need energetic support at every stage, from basal economy to peak demand (activation, proliferation and antibody production). When cancer develops, however, this orderly process breaks down and the balance between ROS and antioxidant is destroyed. If metabolic control fails, the B cell’s specific functions may take the wrong way and acquire pro-tumorigenic features.

For further questions, please contact:

Davide G. Franchina, PhD Student
Experimental and Molecular Immunology, Department of Infection and Immunity,
Luxembourg Institute of Health (LIH)
29 rue Henri Koch
Esch-sur-Alzette
Luxembourg
Davide.franchina@lih.lu