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

Abstract

SummaryVDJ and VJ rearrangements, expression of RAG-1, Tdt and VpreB, and the presence of signal joint circles (SJC) were used to identify sites of Bcell lymphogenesis. VDJ, VkJk but not VjJj 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. VkJk rearrangements but not VjJj rearrangements were recovered from fetal liver at 30-50 DG. SJC were pronounced in bone marrow at 95 DG where VjJj rearrangements were first recovered. The VkJk rearrangements recovered at 20-50 DG used some of the same Vk and Jk 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 VkJk 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.

B Cell Lymphogenesis in Swine Is Located in the Bone Marrow

“…However, pigs, together with all other ungulates, were speculated for .30 y to belong to species that use ileal Peyer's patches for development of B cells (10,11,25). We have previously shown that ileal Peyer's patches are not required for B cell development and maintenance (12)(13)(14), and that this role has probably been filled by the BM (26)(27)(28)(29)(30). In the present study we have finally shown that B cell lymphogenesis in pigs clearly occurs in the BM.…”

The enigma of the lower gut-associated lymphoid tissue (GALT)

“…Monitoring the light-chain repertoire is also simplified, as two V genes and one J comprise 80% of the repertoire, and three V and one J gene account for Ͼ70% of the repertoire [28,63]. Combined with studies on single joint circle, the sites of B cell lymphogenesis can be identified [64]. Altogether, the piglet arguably provides a far more manageable model to address issues concerning immunologic ontogeny, including the role of the IPP, than either rabbits or sheep.…”

“…8). IPP are also not a site of B cell lymphogenesis, as B cell lineage populations in the IPP do not resemble developing B cell lineage cells in the BM [67], and signal joint circles are absent [64,77]. On the other hand, the BM was shown to be fully capable of B cell lymphogenesis and remains active at least for the same period of time as is speculated for the IPP [39, 64, 78 -80].…”

“…Lymphogenesis of B-1 cells is determinant; i.e., B cell levels are maintained by mitotic proliferation, unlike conventional B cells that are produced continuously in BM throughout life [90]. Interestingly, B cell lymphogenesis in rabbit BM wanes in a few months [91], and similar waning occurs in swine, as measured by disappearance of signal joint circles [64]. B cell lymphogenesis in chickens is also determinant [92].…”

Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse

“…Two Ig light chains, kappa and lambda, are used in mammalian species and until recently it was accepted that the lambda light chain gene locus only rearranged if the kappa rearrangement was unsuccessful, although the lambda gene locus may be active before kappa in pigs (Hieter et al, 1981, Sun et al, 2012). It is intriguing that the relative abundance of kappa (κ) and lambda (λ) light chain varies among species: 95% κ/ 5% λ in mice, 66% κ/ 34% λ in humans, 52% κ/ 48% λ in pigs, 9% κ/ 91% λ in cows, 8% κ/ 92% λ in horses, and lambda light chain is the only one expressed in chickens and ducks (Hood et al, 1967, Gibson 1974, Kessler et al, 1981, Reynaud et al, 1985, Magor et al, 1994, Arun et al, 1996).…”