Chimerism a natural ability to tolerate kin, evolutionary traits connecting mammalian and protochordates

• Main Author: A Voskoboynik
• Format: Article
• Language: English
• Published: University of Modena and Reggio Emilia 2009-03-01
• Series: Invertebrate Survival Journal
• Subjects: chimerism; immunologic tolerance; stem cells; tunicate; mammalian pregnancy; Fu/HC; uterine NK
• Online Access: http://www.isj.unimo.it/articoli/ISJ-Suppl-002.pdf

In the middle of the 20th century, Owen (1945, 1954) and Billingham et al. (1953) immunological studies suggested that fetal exposure to foreign antigens during pregnancy induce immunologic tolerance in the fetus. Recently, Mold et al. found that a substantial number of maternal cells crosses the placenta to reside in fetal lymph nodes and induces the development of regulatory T cells (Tregs) that suppress fetal anti-maternal immunity. These Tregs cells persist till, at least, early adulthood. This result demonstrates how chimerism induces fetal tolerance to maternal antigens during mammalian pregnancy. Natural chimerism is the coexistence of two or more genomic lineages within the same individual. It is a common phenomenon which can be detected in a wide variety of multi-cellular organisms. In mammals, natural chimerism can be established during pregnancy between the mother and the fetus or between fetuses in a multiple embryos pregnancy. Restriction of natural chimerism mainly to kin is also observed in colonial marine protochordates. In protochordates, like Botryllus schlosseri, natural chimerism can be established through fusion of vasculature, between a parent colony and its progeny or between siblings (adult distinct colonies).The ability to tolerate a partial allogeneic individual and to create a chimeric entity between these colonies is determined by a single, highly polymorphic, fusion/histocompatibility locus (Fu/HC). Colonies that share at least one allele in their Fu/HC locus would fuse upon contact. A pair that does not share any Fu/HC allele would not. In the chimera, cells transmigrate between partners and in some cases, replace the germline and/or the somatic tissues of the host. This genotype replacement is mediated by stem cells (termed somatic/germ cell parasitism). Botryllus colonies propagate asexually through budding, therefore somatic stem cell parasitism in host colonies can induce the development of a partial allogeneic entity (buds) within the host colony. In this way, chimerism in protochordates serves as a state that enables the development of a “virtual embryo” within the host colony. In light of Mold et al., study, which demonstrates a role to chimerism in tolerance induction during pregnancy, studying the immunological mediators for natural acceptance of partial allogeneic allograft in protochordates may reveal the evolutionary precursors to the tolerance state during mammalian pregnancy.