Elevation of Beta-2 Microglobulin during Prion Infection is Closely Correlated with PrPSc Accumulation and is Independent of MHC-I.

β2-microglobulin (B2M) is implicated in neuroinflammatory and neurodegenerative processes, but its role in prion diseases remains unclear. Here, the alterations in B2M expression and distribution as well as its correlation with PrPSc accumulation were investigated in several scrapie-infected rodent models and a prion-infected cell line. Markedly increased B2M levels were detected in the brains of prion-infected rodents at the terminal stage, as well as in the prion-infected SMB-S15 cells, with prominent colocalization with neurons and microglia. Transient overexpression of cytosolic abnormal PrP in cultured cells induced an increase in B2M, whereas the expression of wild-type PrP did not alter the B2M level. Resveratrol-induced clearance of PrPSc in SMB-S15 cells sufficiently reversed the increased level of B2M. Molecular interactions and histological spatial distributions between B2M and PrPSc were identified in scrapie-infected brains. The B2M upregulation during prion infection was independent of the MHC-I expression. Routine Western blot and ELISA failed to find significant differences in B2M levels between the cohorts of human prion disease (PrD) and non-PrD in cerebrospinal fluid (CSF), and between the cohorts of PrD and the normal population in serum. These findings suggest that prion infection and abnormal PrP accumulation induce remarkable B2M upregulation, and this interaction along with its MHC-I-independent upregulation highlights the potential of B2M in the pathological progression of prion diseases, providing a novel molecular basis for understanding prion-induced neuroinflammation.