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


  • A Voskoboynik Institute of Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, Stanford, USA and Department of Developmental Biology, Stanford University Hopkins Marine Station, Pacific Grove, USA


chimerism, immunologic tolerance, stem cells, tunicate, mammalian pregnancy, Fu/HC, uterine NK


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.