Restricted expression of new guanine nucleotide exchange factor Zizimin2 in aged acquired immune system

The activity of various biological functions, such as nervous, endocrine and immune systems including acquired immunity, is known to decline along with aging. To elucidate the molecular mechanism of this phenomenon, we here compared the number of thymocytes, splenocytes, and bone marrow lymphocytes in young and aged mice and found the age-related functional fragility of the immune system. However, the molecular mechanisms or even the key molecules remain elusive. Therefore, we further focused on a candidate for immunosenesence-related molecules, Zizimin2, which we have recently isolated and identified as a novel guanine nucleotide exchange factor that is highly expressed in murine splenic germinal center B cells after immunization with a T cell-dependent antigen. Here, we showed that endogenous Zizimin2 protein as well as mRNA expression levels in immune organs are strictly suppressed in aged mice. We further observed that the serum antigen specific antibody response is hampered in aged mice compared to that in young animals. Moreover, the Zizimin2 mRNA expression level was not activated after immunization in aged mice. Taken together, these data suggested that Zizimin2 is associated with the reduction of immune response in acquired immunity along with aging.