Older people around the world clearly seem to be more vulnerable to COVID-19, and vaccines are somewhat less effective in protecting them. Why? Researchers at the Rappaport Faculty of Medicine at the Technion-Israel Institute of Technology in Haifa discovered the answer, explored the aging process of the immunes system, and presented ways to rejuvenate it. The findings have been published in Blood under the title “Peripheral B-cells repress B-cell regeneration in aging through a TNFα/IGFBP-1/IGF1 immune-endocrine axis.”

Memory B lymphocytes are cells within the human body that are responsible for long-term production of effective antibodies. They are formed when the body is exposed to a new pathogen (such as a virus or other microbe). Upon consequent exposures to the same pathogen, they recognize it and elicit an enhanced antibody response to trigger an accelerated and augmented immunity. 

These cells are long-lived, capable of surviving and maintaining immune memory for many years. They are what vaccines attempt to generate, providing the body with a first exposure to what it interprets as the pathogen. In her doctoral thesis under the guidance of Prof. Doron Melamed, Reem Dowery studied the problem. 

The team found that as with many other systems in the body, the immune system maintains a steady-state called homeostasis. It turns out that existing memory B lymphocytes, by means of hormonal signals, impede the production of new ones. 

As a result, with age the human immune system becomes more skillful in responding to pathogens it had encountered before, but less capable of adapting to new threats. The same process makes vaccines less effective in protecting the elderly population.

With this explanation revealed and the signalling pathway through which the phenomenon occurs explained, the researchers wondered, could it be possible to alter, to rejuvenate the immune system? To answer that question, Melamed’s lab team collaborated with the departments of hematology and rheumatology in the Tel Aviv Sourasky Medical Center and Haifa’s Rambam Medical Center. 

As part of treatment for some medical conditions (among them lupus, lymphoma, and multiple sclerosis), patients undergo B-cell depletion. In other words, a significant amount of memory B lymphocytes are removed from their body. Examining elderly patients who underwent this procedure, the group found their immune system rejuvenated, and their body able to produce new high potent B lymphocytes once again.

An effect similar to B-cell depletion can be produced by inhibiting one of the hormones in the signalling pathway that supresses the production of new memory B lymphocytes. This ground-breaking proof-of-concept study of Dowery and Melamed has opened the way for exploring the rejuvenation of the immune system. Its more immediate implications are on understanding the immune response in elderly population and providing the correct disease-preventive measures in light of this new information, in particular with regard to the current COVID-19 epidemic.