Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/18/2000
Publication Date: 12/20/2000
Citation: Butler, J.E., Weber, P., Sinkora, M., Sun, J., Ford, S.J., Christenson, R.K. 2000. Antibody repertoire development in fetal and neonatal piglets. II. Characterization of heavy chain complementarity-determining region 3 diversity in the developing fetus. Journal of Immunology. 165(12):6999-7010. Interpretive Summary: In mammals, development of the immune system is critical to survival and normal growth and development. Immune system development in swine and other livestock species is unstudied as compared to more commonly studied humans and mice. Fetal liver was collected from day-23 to -40 porcine fetuses and spleen samples were collected from day-40 and older porcine fetuses. DNA amplification and cloning was completed with leucocytes recovered from liver in day-30 and -40 fetuses and with whole tissues in older fetuses. Findings show that certain features of the porcine fetal heavy chain CDR3 repertoire follow a similar pattern to those described in mice, human, and rabbits, while reaffirming that not all paradigms concerning development of pre-immune repertoire that are based on studies in mice and humans are applicable to pigs. Characterization of developmental changes in pig immunity are important to the swine and veterinary industries for improving neonatal pig survival and developing o specific protective immunity systems (disease vaccination protocols) for neonatal pigs.
Technical Abstract: These studies revealed several features of CDR3 diversity in the porcine pre-immune repertoire. First, N-region additions are as extensive in VDJ rearrangements recovered at 30 d as those in late term fetuses suggesting that Tdt is fully active at the onset of VDJ rearrangement. Second, nearly 90% of all rearrangement is in-frame until late gestation. Third, the age-dependent change from an apparent oligoclonal CDR3 repertoire at 30 d to a polyclonal repertoire is modest while the frequency of duplicate clone recovery indicates that the B-cell compartment expands rapidly between 60 and 70 d. Fourth, there is almost no individual variation in CDR3 spectratype and no striking differences in the CDR3 spectratype among different lymphoid tissues with the exception of the thymus. Finally, while there is some tendency for usage of the most JH proximal and shortest DH segment (DHB) to decreases during the 84-d developmental period, the longer rDH segments are trimmed to the same length as the shorter DH when used in CDR3. Collectively, these findings show that certain features of the porcine fetal heavy chain CDR3 repertoire follow a similar pattern to those described in mice, humans and rabbits, while reaffirming that not all paradigms concerning development of pre-immune repertoire that are based on studies in mice and humans are applicable to all mammals.