We previously found a cross-reactive autoantibody that bound to bovine serum albumin generated in a D-galactose-induced aging mouse model. Also, we confirmed that other reducing sugars (glucose and fructose) could induce the formation of autoantibody, and only following subcutaneous injection, not oral or intraperitoneal administration. Mice that had never been exposed to bovine serum albumin produced an anti-bovine serum albumin autoantibody following repeated subcutaneous injection of D-galactose (D-gal). In this study, we investigated the involvement of the adaptive immune system in the production of this autoantibody. In particular, we examined bovine serum albumin-induced splenocyte proliferation and bovine serum albumin-induced active cutaneous and systemic anaphylaxis in D-gal-treated mice. We find our results particularly interesting: bovine serum albumin stimulates splenocyte proliferation and induces both active cutaneous and systemic anaphylaxis in D-gal-treated mice. In summary, our results suggest that adaptive immune response participates in the autoantibody formation against bovine serum albumin in D-gal-treated mice.