BHF ALELIC POLYMORPHISM DETERMINES CHIMERIC STATE STABILITY IN BOTRYLLUS SCHOLSSERI
Ayelet Voskoboynik, Stanford University
Ayelet Voskoboynik1,2 Mark Kowarsky3, Benyamin Rosental1,2, Aaron M. Newman1, Kohji Hotta4, Katherine J. Ishizuka1,2, Karla J. Palmeri1,2, Norma F. Neff5, Stephen R. Quake5,6 & Irving L. Weissman1,7
1. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, USA.
2. Hopkins Marine Station, Stanford University, USA.
3. Department of Physics, Stanford University, USA.
4. Department of Biosciences and Informatics, Keio University, Japan.
5. Chan Zuckerberg Biohub, USA.
6. Departments of Applied Physics and Bioengineering, Stanford University, USA.
7. Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, USA.
Histocompatibility is the basis by which multicellular organisms of the same species distinguish self from nonself. To gain insights into the evolution and molecular characteristics of allorecognition, we are studying Botryllus schlosseri a member of the tunicates. B. schlosseri that engages in a natural transplantation reaction, whereby self-recognition between colonies leads to the formation of chimeras with shared vasculature (fusion), and a non-self recognition results in rejection. Progeny from crosses between histocompatible B. schlosseri colonies are known to segregate as expected from a monogenic trait. We have found a polymorphic gene, called BHF, or Botryllus histocompatibility factor, that governs fusion or rejection outcomes between Botryllus colonies. Colonies fuse if they share one or both BHF alleles AB=AB or AB=BC and reject each other if there are no alleles in common, e.g. AB=CD (Voskoboynik and Newman et al. 2013). Following fusion, one chimeric partner is often eliminated in a process of allogeneic resorption
(Corey and Rosental et al. 2016). But stable chimerism where both partners thrive also occurs. Here based on long term studies aims to characterize molecular and morphological phenotypes of chimeras we provide evidence that BHF, and genes that promote immune response and cell death, are highly expressed in the eliminated chimeric partner. Furthermore, the level of allelic differences between the non-shared BHF allele (e.g. A vs. C in AB=BC chimera) determines shortterm/ stable chimerism phenotypes. Just as HLA haplotyping predicts the success of organ transplantation in humans, BHF haplotyping can predict both fusion/rejection outcomes and, loss of tolerance in the Botryllus chimera