Development of the neonatal B and T cell repertoire in swine: implications for comparative and veterinary immunology

Abstract

-Birth in all higher vertebrates is at the center of the critical window of development in which newborns transition from dependence on innate immunity to dependence on their own adaptive immunity, with passive maternal immunity bridging this transition. Therefore we have studied immunological development through fetal and early neonatal life. In swine, B cells appear earlier in fetal development than T cells. B cell development begins in the yolk sac at the 20th day of gestation (DG20), progresses to fetal liver at DG30 and after DG45 continues in bone marrow. The first wave of developing T cells is γδ cells expressing a monomorphic Vδ rearrangement. Thereafter, αβ T cells predominate and at birth, at least 19 TRBV subgroups are expressed, 17 of which appear highly homologous with those in humans. In contrast to the T cell repertoire and unlike humans and mice, the porcine pre-immune VH (IGHV-D-J) repertoire is highly restricted, depending primarily on CDR3 for diversity. The V-KAPPA (IGKV-J) repertoire and apparently also the V-LAMBDA (IGLV-J) repertoire, are also restricted. Diversification of the pre-immune B cell repertoire of swine and the ability to respond to both T-dependent and T-independent antigen depends on colonization of the gut after birth in which colonizing bacteria stimulate with Toll-like receptor ligands, especially bacterial DNA. This may explain the link between repertoire diversification and the anatomical location of primary lymphoid tissue like the ileal Peyers patches. Improper development of adaptive immunity can be caused by infectious agents like the porcine reproductive and respiratory syndrome virus that causes immune dysregulation resulting in immunological injury and autoimmunity.

Antibody Repertoire Development in Fetal and Neonatal Piglets. XX. B Cell Lymphogenesis Is Absent in the Ileal Peyer’s Patches, Their Repertoire Development Is Antigen Dependent, and They Are Not Required for B Cell Maintenance

“…Our studies do not support the 25-y-old paradigm described in reviews (23,35,37) that the IPP is a "mutant breeding organ" (80) and as such a bursal equivalent, as proposed by Morris and Reynolds (6) and then reinforced by the studies of Reynaud et al (33,34) and others (14,35). Our studies on SHM and repertoire diversification in the IPP of DG 95 fetuses and in GF animals revealed that the magnitude of SHM and repertoire diversification were the same or lower than in other lymphoid tissues examined (Figs.…”

“…Further studies by Griebel et al (35) supported this view by showing that B cells in the IPP underwent rapid negative selection similar to BM B cells and those in the avian bursa. These and other observations concerning the IPP, rabbit appendix, and the bursa of Fabricius have been molded into a paradigm regarding a role for hindgut lymphoid tissue that is embedded in textbooks and reviews (36,37).…”

“…Thus, using the piglet as a model to study the role of the IPP of artiodactyls is appropriate but more importantly permits improvements to the experimental design. The fetal B and T cell repertoires of both species develop without maternal influence and regulatory factors such as maternal IgG that are known to influence fetal immunological development in mice and rabbits (37)(38)(39)(40)(41). However, swine have multiple offspring (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), weigh ,2 kg at birth, and can be conveniently reared in GF isolators after their recovery by cesarean surgery where all environmental and maternal factors are thereafter controlled by the experimenter (41,42).…”

Membrane markers of the immune cells in swine: an update

“…Specific identification of the various subpopulations of leukocytes enables improved investigations of the immune response to various porcine infections such as Actinobacillus pleuropneumoniae, African swine fever virus, classical swine fever virus, porcine reproductive and respiratory syndrome virus (PRRSV) and Aujeszky disease virus [6, 41,76,110,116,127,137,213]. An understanding of these interactions is essential for the development of new generations of vaccines.…”

“…The unique aspect of T cell biology in the pig makes this species particularly suitable for studying the generation of T cell subset diversity and tissue distribution. Pigs have been used, since 1966, to study the ontogenesis of the immune response [41,156,201,227] within a foetal development not influenced by maternal antibodies and antigens. These studies concluded that piglets are immunocompetent at birth [22], albeit with a largely 'immature' immune system that has not been previously in contact with antigens, resulting in a primary immune response, a less developed mucosal immune response and lower repertoire diversity than in adults [182].…”