The absence of human beta 2-microglobulin increases the occurrence of ankylosing enthesopathy in HLA-B27 transgenic mice.

HLA-B27 transgenic mice develop a spontaneous ankylosing enthesopathy (ANKENT). We have investigated the occurrence of ANKENT in transgenic mice carrying transgenes for human beta 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 beta 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 beta 2-microglobulin suggests a possible role for impaired cell surface expression of HLA-B27. The absence of human beta 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.