Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/6/2002
Publication Date: 2/15/2003
Citation: SINKORA, M., SUN, J., SINKOROVA, J., CHRISTENSON, R.K., FORD, S.P., BUTLER, J.E. ANTIBODY REPERTOIRE DEVELOPMENT IN FETAL AND NEONATAL PIGLETS. VI. B CELL LYMPHOGENESIS OCCURS AT MULTIPLE SITES WITH DIFFERENCES IN THE FREQUENCY OF IN-FRAME REARRANGEMENTS. JOURNAL OF IMMUNOLOGY. 2003. v. 170(4). p. 1781-1788. Interpretive Summary: In mammals, development of the immune system is critical to survival and normal growth and development. Development of the immune system appears to be different in swine and other livestock species than in more commonly studied humans and mice. Characterization of the immune systems during fetal development can lead to improved understanding of protective immunity in newborns. B cell lymphogenesis in mammals occurs in various tissues during development but it is generally accepted that it operates by the same mechanism in all tissues. Yolk sac, liver, spleen, early thymus, bone marrow, and late thymus were studied from developing swine fetuses. Cell suspensions, cloning and sequence analysis were performed. Results suggest that gene (VDJ) rearrangement differs among yolk sac, liver, spleen, early thymus, bone marrow, and late thymus fetal tissues in swine. These findings indicate there are multiple sites of B cell lymphogenesis in fetal piglets and differences in the frequency of productive VDJ rearrangements at the various sites. Characterization of developmental changes in pig immunity are important to the swine and veterinary industries for improving neonatal pig survival and developing of specific protective immunity systems (disease vaccination protocols) for neonatal pigs.
Technical Abstract: B cell lymphogenesis in mammals occurs in various tissues during development but it is generally accepted that it operates by the same mechanism in all tissues. We show that in swine, the frequency of in-frame (IF) VDJ rearrangements differs among yolk sac, fetal liver, spleen, early thymus, bone marrow, and late thymus. All VDJ rearrangements recovered and analyzed on the 20th day of gestation (DG20) from the yolk sac were 100% IF. Those recovered at DG30 in the fetal liver were >90% IF, and this predominance of cells with apparently a single IF rearrangement continued in all organs until approximately DG45, which corresponds to the time when lymphopoiesis begins in the bone marrow. Thereafter, the proportion of IF rearrangements drops to approximately 71% (i.e., the value predicted whether VDJ rearrangement is random and both chromosomes were involved). Unlike other tissues, VDJs recovered from thymus after DG50 display a pattern suggesting no selection for IF rearrangements. Regardless of differences in the proportion of IF rearrangements, we observed no significant age- or tissue-dependent changes in CDR3 diversity, N region additions, or other characteristics of fetal VDJs during ontogeny. These findings indicate there are multiple sites of B cell lymphogenesis in fetal piglets and differences in the frequency of productive VDJ rearrangements at various sites. We propose the latter to result from differential selection or a developmentally dependent change in the intrinsic mechanism of VDJ rearrangement.