Antibody repertoire development in swine

Swine belong to the Order Artiodactyla and like mice and humans, express IgM, IgD, IgG, IgE and IgA antibodies but a larger number of IgG subclasses. Like rabbits and chickens, expressed V_H genes belong to the ancestral V_H3 family and only 5 comprise >80% of the pre-immune repertoire. Since they use primarily two D_H segments and have a single J_H like chickens, junctional diversity plays a relatively greater role in repertoire formation than in humans and mice. Proportional light chain usage surprisingly resembles that in humans and is therefore distinctly different from the predominant kappa chain usage (>90%) of lab rodents and predominant lambda chain usage in other ungulates (>90%). The pre-immune V_k repertoire also appears restricted since >95% of V_kJ_k rearrangements use only a few members of the IGKV2 family and only J_k2. Two V families (IGLV3 and IGLV8) are used in forming the pre-immune repertoire. Antibodies that do not utilize light chains as in camelids, or the lengthy CDR3 regions seen in cattle that use V_H4 family genes, have not been reported in swine. B cell lymphogenesis first occurs in the yolk sac but early VDJ rearrangements differ from mice and humans in that nearly 100% are in-frame and N-region additions are already present. Swine possess ileal Peyers patches like sheep which may be important for antigen-independent B cell repertoire diversification. The presence of pro B-like cells in interlobular areas of thymus and mature B cells in the thymic medulla that have switched to especially IgA in early gestation, is so far unique among mammals. The offspring of swine are believed to receive no passive immunity in utero and are precosial. Thus, they are a useful model for studies on fetal–neonatal immunological development. The model has already shown that: (a) colonization of the gut is required for responsiveness to TD and TI-2 antigens, (b) responsiveness due to colonization depends on bacterial PAMPs and (c) some viral pathogens can interfere with the establishment of immune homeostasis in neonates. Studies on swine reinforce concerns that caution be used when paradigms arising from studies in one mammal are extrapolated to other mammals, even when similarities are predicted by taxonomy and phylogeny. Swine exemplify a situation in which evolutionary diversification of the immune system is not characteristic of an entire order or even of other related systems in the same species.

Keywords:Swine, B cells, Immunoglobulins, Ontogeny, Fetal, Colonizing bacteria, TLR ligands, Thymus,Artiodactyla,amino acids,taxonomy.

Corresponding author: Tel +1 319 335 7776; fax +1 319 335 9006

E-mail: john-butler@uiowa.edu