While the specific humoral response of reptiles is slow and does not typically increase in titer or binding affinity upon secondary immunization, reptiles produce polyreactive natural antibodies (NAbs) that have low binding affinity and are produced in the absence of antigen stimulation. Given the poor specific response, NAbs may be an important protective resource in reptiles. In order to investigate the relative contributions of natural and specific antibodies, we immunized turtles with the novel antigen keyhole limpet hemocyanin (KLH). We did not detect an increase in antibody titers. However, preimmunization titers to KLH, as well as to a series of other novel antigens, were high in the turtles, indicating a strong NAb response. Interestingly, we found an age-associated increase in NAb titers in adults. Overall, our data suggest that reptiles may use NAbs as part of a strong innate immune response rather than relying on slower specific humoral responses. 1. Introduction The vertebrate immune system is a complex network of cells and molecules that interact to protect the animal against constant attacks from pathogens. Upon initial contact with an antigen, the nonspecific innate branch of the immune system responds quickly to act as a first line of defense [1]. At this time there is also activation of the humoral branch, which involves the production of highly specific antibodies by B cells. Antibodies are important in protecting against pathogens because of their role in facilitating lysis of microorganisms, neutralizing toxins, and agglutinating microorganisms to improve phagocytosis [2]. Humoral responses are often studied by deliberately immunizing na？ve animals with an antigen to which they have not been exposed previously (a novel antigen) and then examining the resulting antibody response. The kinetics of the humoral response to immunization is well studied in mammals and, to a lesser extent, in birds. When exposed to a novel antigen, a latent phase occurs in which T and B cells first make contact with the antigen and begin to proliferate and differentiate. In mammals, this latent period lasts around 1 to 2 weeks depending on such factors as type and dose of antigen used and immunization route. In birds, the latent period is around 3 to 5 days depending on the species [3]. After the latent period, antibody titers increase exponentially and peak at a steady state shortly thereafter. During this phase, IgM is the first antibody produced, which is then supplanted by IgG in mammals and IgY in birds [4]. After reaching peak titers, antibody
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