An Addendum to the Destructive Rejuvenation of B Cell Immune Function

You might recall that researchers published earlier this year on a demonstration of the ability to rejuvenate B cell populations in old mice and thereby improve failing immune function. This was achieved by essentially culling the cells - which fits in with the idea that much of what is wrong with the aging immune system involves the configuration of the controlling biological programs, not incapacity of the cells themselves or of the ability of the body to produce new cells.

Collectively, our results suggest that immunosenescence in the B-lineage is not irreversible, and that depletion of the long-lived B cells in old mice rejuvenates the B-lineage and enhances immune competence. .... depletion of B-cells in old mice was followed by expansion of [populations of progenitor cells that create B-cells and] a revival of [lymphopoiesis, or the creation of B-cells] in the bone marrow, and generation of a rejuvenated peripheral compartment that enhanced the animal's immune responsiveness to antigenic stimulation.

The same research team has put out another more recent paper that adds a little more confirming information to the picture:

Aging is accompanied by a decline in B lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. The mechanisms underlying these changes are unclear. To explore whether aging in the B lineage is subjected to homeostatic regulation, we used mutant mice bearing chronic B cell deficiency from birth. We show that chronic B cell deficiency from birth [prevents] age-related changes in the B lineage. Thus, frequencies of early and late hematopoietic stem cells, B lymphopoiesis, and the rate of B cell production do not substantially change with age in these mice, as opposed to wild-type mice where kinetic experiments indicate that the output from the bone marrow is impaired. Further, we found that long-lived B cells did not accumulate and peripheral repertoire was not altered with age in these mice. Collectively, our results suggest that aging in the B lineage is not autonomously progressing but subjected to homeostatic regulation.

Which is interesting - mice with effectively ageless (or at least only very slowly aging) portions of their immune system. It suggests that there should be better forms of configuration in our immune systems for long-term use, and that these forms of configuration are not in fact very far removed from what we have now. Presumably these better configurations were not selected for because they were not as effective in the earlier part of life when mammals are fecund and thus evolutionary pressure is greatest. From the point of view of evolutionary success, it only matters how well a biological system operates over the time in which descendants can be created and nurtured: it's all downhill after that.

The bottom line is that selective cell destruction technologies of the sort under development by the cancer research community have great potential as tools to enable immune system rejuvenation. If doing no more than selectively removing very distinctive populations of cells can have a strongly positive outcome, it shouldn't be too many more years before biotech companies start in on this line of work.