Discovery of the radiation-induced bystander effect(RIBE) demonstrates that cell death and genomic instability are not restricted to cells that are directly exposed to ionising radiation(IR). The RIBE refers to a situation where cells that have not been directly exposed to IR behave as though they have been exposed. This phenomenon presents real clinical consequences such as increased risk of secondary malignancies and inflammatory diseases after localised radiotherapy. Past reports indicate pronounced increase of DNA damage in bystander cells, especially in those of highly proliferative tissues. The fluctuations of the host’s immunological response elicited by localised radiation exposure are a proposed mechanism of the bystander effect. Our aim was to establish the contributions of DNA damage response and the immunological components in the propagation of the RIBE, by using synchrotron-generated irradiation of immune- compromised mice. The Imaging and Medical beamline(IMBL) at the Australian Synchrotron made it possible to investigate a new pre-clinical modality, microbeam radiation therapy(MRT), which yields superior therapeutic benefit while also preserving neighbouring healthy tissues in animal models, contrary to the broad beam modality currently used in hospitals. The MRT beam is generated when a single X-ray beam is split by a collimator producing a lattice of planar microbeams. Wild-type C56BL/6 and Balbc mice and immune-compromised mice (macrophage-depleted, CCL2 KO and NSG) were irradiated with 10Gy peak dose of MRT in an 8x8mm area on the right hind leg, with a dose rate of 49Gy/sec. At 3 and 6 days post-irradiation, irradiated skin and unirradiated tissues were collected and probed for DNA damage using the gamma-H2AX assay, apoptotic cell death and local immune response. Pronounced and robust DNA damage, apoptotic events and immunological response were discovered in intestinal crypt cells of wild-type mice indicating the RIBE; these events were compromised in immune-deficient mice. We discuss the role of immune system components in propagation and persistence of genome destabilisation after localised irradiation, in normal tissues distant from the irradiated site.