The Absence of Human β2-microglobulin Increasesthe Occurrence of Ankylosing Enthesopathy in HLA-B27 Transgenic Mice

Summary

HLA- B27 transgenic mice develop a spontaneous ankylosing enthesopathy ANKENT). We have investigated the occurrence of ANKENT in transgenic mice carrying transgenes for human ?2- microglobulin M TGM), HLA-B27-heavy chain 27 TGM), or both 27M TGM). An unexpected finding was the increase in ANKENT occurrence among the HLA- B27 transgenic mice lacking the human ?2- microglobulin transgene 27 TGM): 33% of such mice were found to develop ANKENT, whereas 19% of 27M mice were diseased. In addition, the expression of HLA- B27 molecules in individual 27 TGM was highly variable, ranging from no expression to a level similar to that observed in 27M TGM. Our results confirm that in mice the HLA- B27 transgene is a relative risk factor for ANKENT. The increase of ANKENT occurrence is HLA- B27 transgenics in the absence of human ?2- microglobulin suggests a possible role for impaired cell surface expression of HLA- B27. The absence of human ?2- microglobulin might entail an accumulation of unassembled HLA- B27 heavy chains. Exposure of these mice to an environmental trigger could then lead to an inappropriate immune response which might result in disease development.