Vet. Res. 37 (2006) 417-441
DOI: 10.1051/vetres:2006009

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

John E. Butler^a, Marek Sinkora^b, Nancy Wertz^a, Wolfgang Holtmeier^c and Caitlin D. Lemke<sup>a

a</sup>  Department of Microbiology and Interdisciplinary Immunology Program, The University of Iowa, Iowa City, IA 52242, USA
^b  Czech Academy of Sciences, Novo Hradek, Czech Republic
^c  Medizinische Klinik. I. Johann Wolfgang Goethe-Universität, 60590 Frankfurt am Main, Federal Republic Germany

(Received 29 April 2005; accepted 18 October 2005; published online 9 March 2006)

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 cells expressing a monomorphic V rearrangement. Thereafter, 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.

Key words: fetal / ontogeny / colonization / repertoires / animal model

Corresponding author: John E. Butler john-butler@uiowa.edu

© INRA, EDP Sciences 2006