Antibody repertoire development in fetal and neonatal piglets. XXII. λ Rearrangement precedes κ rearrangement during B-cell lymphogenesis in swine.

VDJ and VJ rearrangements, expression of RAG-1, Tdt and VpreB, and the presence of signal joint circles (SJC) were used to identify sites of B-cell lymphogenesis. VDJ, VλJλ but not VκJκ rearrangements or SJC were recovered from yolk sac (YS) at 20 days of gestation (DG) along with strong expression of VpreB and RAG-1 but weak Tdt expression. VλJλ rearrangements but not VκJκ rearrangements were recovered from fetal liver at 30-50 DG. SJC were pronounced in bone marrow at 95 DG where VκJκ rearrangements were first recovered. The VλJλ rearrangements recovered at 20-50 DG used some of the same Vλ and Jλ segments seen in older fetuses and adult animals. Hence the textbook paradigm for the order of light-chain rearrangement does not apply to swine. Consistent with weak Tdt expression in early sites of lymphogenesis, N-region additions in VDJ rearrangements were more frequent at 95 DG. Junctional diversity in VλJλ rearrangement was limited at all stages of development. There was little evidence for B-cell lymphogenesis in the ileal Peyer's patches. The widespread recovery of VpreB transcripts in whole, non-lymphoid tissue was unexpected as was its recovery from bone marrow and peripheral blood monocytes. Based on recovery of SJC, B-cell lymphogenesis continues for at least 5 weeks postpartum.