HLA-G-ILT2 interaction contributes to suppression of bone marrow B cell proliferation in acquired aplastic anemia.

Abstract

Acquired aplastic anemia (AA) is an autoimmune disease characterized by hematopoietic stem and progenitor cell destruction in bone marrow. The non-classic human leukocyte class I antigen (HLA-) G interacts with multiple cell subsets, such as T cells and B cells. HLA-G exerts powerful immune suppression by binding with its receptors, immunoglobulin-like transcripts (ILTs). Here, we compared 46 AA patients and 28 healthy controls. Soluble HLA-G levels in bone marrow supernatants from AA patients were higher than controls. The proportion of bone marrow B cells was decreased and the ILT2-expressing cells among CD19+ cells were increased in AA patients. In addition, the percentage of mature B cells among marrow B cells was increased in AA patient, while the percentage of pro-B plus pre-B cells was decreased. More immature B cells and pro-B plus pre-B cells expressed ILT2 in AA patients than in controls, while mature B cells expressing ILT2 did not differ significantly. Functional studies demonstrated that high-level soluble HLA-G inhibited bone marrow B cell proliferation by interacting with ILT2 in AA, and was blocked by anti-HLA-G and anti-ILT2 monoclonal antibodies. Together, these results suggest that the abnormal decrease of pro-B plus pre-B cells in AA patients was related to the enhanced suppression by the excess HLA-G and ILT2 proteins. Therapeutic blockade of the HLA-G-ILT2 interaction may help to normalize bone marrow B cell proliferation.