ARS | Publication request: Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine

Submitted to: Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 8, 2012
Publication Date: October 1, 2012
Citation: Sun, X., Wertz, N., Lager, K., Sinkora, M., Stepanova, K., Tobin, Butler, J.E. 2012. Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine. Immunology. 137(2):149-159.

Interpretive Summary: In animals and birds the immune system has two major classes of blood cells known as T cells and B cells. Understanding how these cells develop from conception throughout life can provide strategies that may be used to treat and prevent diseases. This process has been well characterized in several animal models, but little is known about how the immune system develops in swine. The growing importance of swine in biomedical research, and the fact that artiodactyls (even-toed hoofed mammals like pigs) comprise 50% of all mammals including many important food and agricultural species, prompted this study to investigate the development of B cells in pigs. B cell development or lymphogenesis in the mouse and human is continuous throughout life in bone marrow. This is different from the chicken and rabbit where the process stops at birth or shortly thereafter. In this study, B cell lymphogenesis was first detected in porcine fetuses at 20 days of gestation, during later stages of gestation and through the first 5 weeks of life, the scheduled conclusion of the animal studies. Based on initial studies it appears B cell development in the pig begins early in gestation and continues at least through the first weeks of life similar to humans and mice. Additional study will be required to determine if this process in swine continues into adulthood.

Technical Abstract: PCR was used to detect VDJ and VJ rearrangement, expression of RAG-1, TdT and VpreB and the presence of signal joint circles (SJC) in an effort to identify sites of B cell lymphogenesis in tissue lysates and sorted leukocytes of fetal and newborn piglets. VDJ, VlambdaJlambda but not VkappaJkappa rearrangements or SJC were recovered from yolk sac at 20 days of gestation (20 DG) along with strong expression of VpreB and RAG-1 but weak TdT expression. SJC were recovered in fetal liver at 30 DG and strong expression of RAG-1, TdT and VpreB was observed. N-region additions were less frequent at 20 and 30 DG than in bone marrow at 95 DG. SJC were pronounced in BM where VkappaJkappa rearrangements were first recovered and B cell lymphogenesis remained active in bone marrow for at least five weeks postpartum. The widespread recovery of VpreB transcripts in whole, non-lymphoid tissue was unexpected as was its recovery from bone marrow and peripheral blood monocytes. These findings extend our knowledge of B cell lymphogenesis in yet another mammal by showing that: (a) Rearrangement on the lambda locus precedes that of kappa; (b) B cell lymphogenesis continues after birth; (c) Transcripts for RAG-1 and Vpre-B can be recovered from non-lymphoid tissues and (d) Recovery of nuclear SJC appears to be the best indicator of B cell lymphogenesis in piglets.