Some animal scientists regard the small number of animals used in such studies as statistically irrelevant. obtained. Studies on neonatal piglets have (a) provided valuable information on the development of the adaptive immune system, (b) lead to important advances in evolutionary biology, (c) aided our understanding of passive immunity and (d) provided opportunities to use swine to address specific issues in veterinary and biomedical research and immunotherapy. This review summarizes the history of the development of the piglet as a model for antibody repertoire development, thus providing a framework to guide future investigators. Keywords:Swine, Gnotobiotic, Models, Developmental immunology, Review == 1. Introduction == == 1.1. Why the Exo1 piglet model? == Understanding the intrinsic immunological capability of fetal and neonatal mammals can be compromised by transfer of maternal passive antibodies and other factors in utero (Fig. 1). Furthermore, since altricial newborns (rodents and primates) cannot be reared separate from their mothers, it limits the experimental control of external factors that have been shown to impact postnatal development of adaptive immunity (Fig. 2). Some reasons why the piglet is a useful model for studies on development of the adaptive immune system are listed inTable 1. == Fig. 1. == Transfer Exo1 of immunity from mother to young among common placental mammals. Group I and Group III mammals represent the extremes in which receptor-mediated transport of IgG occurs via the placenta (Grp I) versus the mammary gland (Grp III). This difference is reflected in the Ig constituency of the colostrum; font size depicts relative Ig concentrations in colostrum. Uptake by the suckling neonate differs among mammals. In rodents this is mediated by FcRn which transports IgG while among Grp III mammals it is receptor independent (Butler, 1974). == Fig. 2. == The critical window of immunological development. The period between late Exo1 gestation and weaning is depicted as a window in which natural and passive antibodies provide protection to the neonate and when colonization drives the development of adaptive immunity including oral tolerance. The dotted line indicates the period in which natural antibodies are considered important. Occurring in an orderly and regulated fashion, the events during this period create a state of immune homeostasis by the time of weaning (Butler et al., 2006,Butler and Sinkora, 2007). == Table 1. == Characteristics of piglets as models for fetal/neonatal studies. == 1.2. Bumps in the road == Choosing an animal model unless it is the species itself, is complicated by diversity among vertebrates in adaptive immunity.Table 2,Table 3summarize two examples of diversity; diversity among mammals in Ab isotypes and diversity in variable region repertoire. == Table 2. == The C-region repertoire of common mammals. * = Pseudogene; ? = identification not confirmed. == Table 3. == Variable region diversity and light chain usage among mammals. Number of families (F) of variable region genes. JC occurs as duplicons. If the intent is to use swine as models for primates, the situation regarding IgG and IgA subclasses is different. Since subclass diversification occurred after speciation (Butler, 2006,Butler et al., 2008a) a particular subclass in one species has no homology to one of the same name in another mammal unless closely related (sheep/cattle). Because of this evolutionary divergence, mAb and polyclonal antibodies (pAb) specific for a subclass protein in one species do not specifically recognize (cross-react with) an IgG of the same name in another species. This creates a reagent problem and means that in the case of IgG, this isotype must be characterized for each species and suitable species-specific reagents must be prepared (Section2.5). Thus, what is learned about the biological role of IgG1 in mice cannot be extrapolated to IgG1 in swine, humans, cattle, horses, guinea Rabbit Polyclonal to Tyrosine Hydroxylase pigs, etc. Characterizing a new system and preparing new reagents delays application of any model. Therefore choosing the piglet model has meant confronting a reagent problem which indirectly results from failure to understand the diversity of the adaptive immune system..