B cells are an important part of the adaptive immune system, using antibodies to coordinate the T cell response to pathogens and other targets of opportunity that immune cells should attack. As is the case for all aspects of the immune system, B cell function degenerates with age. Growing numbers of what are known as age-associated B cells emerge. These are known to contribute to autoimmunity at the very least, by inappropriately rousing the immune system to attack a patient's own tissues.

What to do about this? Getting rid of the problem cells seems like a good idea. It was some years ago that researchers first demonstrated that targeted destruction of B cells can reverse measures of B cell aging in old mice. The old B cells presumably include damaged, misconfigured, and other problem cells beyond the age-associated B cells mentioned above. Depleting the B cell population triggers the aggressive generation of new B cells, and the new cells generally lack the problems of the old ones.

Does this produce an actual improvement in immune function, though? We would expect it to eliminate some autoimmune issues, and reduce the risk of occurrence going forward, but does the immune response get better? In today's open access paper, researchers demonstrate that the answer is no. This may well be for the same reason that regeneration of the thymus doesn't improve overall immune function in late life in mice and non-human primates, which is that lymph nodes degenerate to the point at which the immune system cannot effectively use the lymphatic system as a point of coordination, even when the coordinating cells have been restored and refreshed. Aging is a matter of damage in all components of any system, and while in some cases incremental benefit can be produced by fixing any one component, in others it might require more than that.

Fortunately, lymph node degeneration appears inflammatory and fibrotic in nature, features of aging that are convincingly linked to the presence of senescent cells. This dysfunction of the lymphatic system may well be something that can be addressed or pushed back sufficiently via senolytic treatments to allow incremental repairs of other components of the immune system to be individually effective. That includes replacement of B cells, removal of damaged and harmful T cell populations, regrowth of the thymus, and regeneration of the hematopoietic stem cell population. Each of those is a sizable project.

Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging