Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2002
Publication Date: 9/10/2002
Citation: BUTLER, J.E., SUN, J., WEBER, P., FORD, S.P., REHAKOVA, Z., SINKORA, J., FRANCIS, D., LAGER, K.M. SWITCH RECOMBINATION IN FETAL PORCINE THYMUS IS UNCOUPLED FROM SOMATIC MUTATION. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY. 2002. v. 87. p. 307-319. Interpretive Summary: Porcine reproductive and respiratory syndrome (PRRS) is a viral disease of swine caused by the PRRS virus. This disease was first recognized in the late 1980s and since then it has become the number one infectious disease concern of the swine industry. The PRRS virus will cause reproductive failure in the sow herd (infertility, abortions, stillborn and weak-born pigs) and respiratory disease that is most severe in young pigs. Although there has been considerable research investigating different aspects of PRRS, there are still many unknowns about this disease. One such area is PRRS virus immunology. A research goal at the National Animal Disease Center is to balance applied and basic research programs to achieve the best combination of work that can benefit the customers or stakeholders of that research, in this case the US swine industry. This paper describes basic research investigating the development of the porcine immune system by analyzing fetal porcine tissues. It is anticipated that a better understanding of how the immune system develops will provide insight into how one might adapt the development of the immune system to improve current vaccine programs or improve current vaccines so they might be more safe and efficacious. This area of study is particularly relevant for PRRS since current vaccines are not fully protective.
Technical Abstract: Since fetal serum Ig isotype profiles suggested that IgG and IgA could be of de novo origin, we studied their transcription and secretion. IgM transcripts were present at 50 days of gestation in major fetal lymphoid tissues, IgG and IgA transcription was pronounced at 60 days in fetal thymus and both transcription and secretion in this organ increased in late fetal life. The CDR3 spectratype of thymic IgG and IgA transcripts was as polyclonal as that of IgM already at 70 days in utero indicating a broad repertoire of switched B-cells. However, VDJs transcribed with the switched isotypes were not hypermutated as were those from immunized fetuses, indicating that switch recombination and somatic mutation are not coupled in utero in piglets. This finding and the fact that the oligoclonal IgA and IgM repertoires in a non-inductive site of the mucosal immune system (parotid gland) becomes polyclonal in piglets reared germ-free, suggest that initial expansion of switched B-cells in fetal and neonatal piglets is not driven by environmental antigen. Our findings collectively suggest that all IgA and IgM may result from de novo synthesis while some IgG probably results from selective transport. The latter is consistent with the gradual decline in serum IgG concentration in germ-free isolator piglets and the expression of FcRn in the porcine placenta.