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Every cell displays samples of what is inside it on its surface, on structures the immune system inspects. B2M is a necessary part of those structures — delete it and the display disappears, so the recipient's T cells cannot identify the cell as foreign. The catch is that natural killer cells are specifically alarmed by cells with no display, which is why hypoimmune designs add a second signal to reassure them.
B2M, at 15q21.1, encodes beta-2 microglobulin, an obligate component of MHC class I. Knockout abolishes surface class I expression, evading CD8 T-cell recognition of allogeneic cells, but triggers natural killer 'missing self' surveillance — which hypoimmune platforms counter by overexpressing CD47 or retaining HLA-E.
Sources
- New England Journal of Medicine · 2025
Survival of transplanted allogeneic beta cells with no immunosuppression ↗