We previously reported (Olkhanud et al, Vaccine, 2011) that, by modifying a vaccine formulation, we devised Alzheimer's disease (AD) vaccine, termed Abeta-CoreS. The vaccine induces a potent humoral response and alleviates AD even if used at the onset of the disease, i.e. in old mice when traditional vaccines are ineffective. The study suggests the importance of targeting B cells and T cells. The aging-associated B cell impairment can be circumvented by modifying vaccines. We recently found that the B-cell impairment affects T cell responses and be a cause of expansion of effector CD8+T cells in tumor-bearing mice. Here, by extrapolating the same mechanism in aging, we discovered a new type of B cells, termed 4BL cells, that accumulates in old age of mammals, such as humans, monkeys, and mice. The clinical importance of 4BL cells is that they induce autoimmune CD8+ T cells, which also accumulate in old age of people. The biological/immunological importance of this finding is that it underscores B cells, but not the classic antigen-presenting cells - dendritic cells, as inducers of potentially autoimmune CD8+ T cells. We provide a mechanistic insight on the existence of pathogenic B cells as inducers of age-associated immunological dysfunctions. I believe that this finding, which we recently reported in Blood (Lee Chang et al., 2014), will attract significant attention in the field. Despite attractiveness of our discovery for potential commercial applications, recent changes in the patenting law precludes its patenting. We also report that impaired B-cell function in the elderly can be therapeutically circumvented. Utilizing our recently developed 4BL-tareging strategy, we were able to repair the age-associated immunological impairments, suggesting that the process is reversible. The elimination of 4BL cells causes the loss of autoimmune CD8 T cells. Moreover, B cells can also be rejuvenated via induction of de novo B-cell lymphopoiesis in old mice. We also explored possibilities to inactivate functions of B cells utilizing resveratrol (RSV, a polyphenol originally extracted from red wine). Our modeling studies in tumor-bearing mice indicate that RSV inactivates tBregs. As a result, RSV efficiently blocks immune escape and metastasis of highly aggressive 4T1 breast cancer. The RSV-treated mice also elicited cancer-neutralizing effector CD8+ T cells due to the loss of suppressive activity of tBregs and their inability to induce conversion of Tregs. The study has been recently published (Lee-Chang et al., 2013).
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