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

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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.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (91942306, 81770133, 81800112), China Postdoctoral Science Foundation (2020M672075).

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Authors and Affiliations

  1. Department of Hemodialysis, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Yuan-xin Sun

  2. Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Qi Feng, Shu-wen Wang, Xin Li, Zi Sheng & Jun Peng

  3. Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Qi Feng, Shu-wen Wang & Xin Li

  4. School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China

    Zi Sheng

  5. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    Jun Peng

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  1. Yuan-xin Sun
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  2. Qi Feng
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  3. Shu-wen Wang
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  4. Xin Li
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  5. Zi Sheng
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Contributions

All authors contributed to the study conception. J.P. designed the research, performed the research, analyzed the data, and wrote the paper; Y.-x.S. performed the research, analyzed the data, and wrote the paper; Q.F., S.-w.W., X.L., and Z.S. performed the research and analyzed the data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zi Sheng or Jun Peng.

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The research protocol was established according to the ethical guidelines of the Helsinki Declaration and was approved by the Medical Ethics Committee of Qilu Hospital, Shandong University.

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A portion of this study was presented under the title, “Aberrant Expression Profiles of HLA-G and Immunoglobulin-like Transcripts (ILTs) in Acquired Aplastic Anemia” (Abstract Code: P248) and awarded a travel grant at the 20th Congress of European Hematology Association in Vienna, Austria, June 11–14, 2015

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Sun, Yx., Feng, Q., Wang, Sw. et al. HLA-G-ILT2 interaction contributes to suppression of bone marrow B cell proliferation in acquired aplastic anemia. Ann Hematol 101, 739–748 (2022). https://doi.org/10.1007/s00277-022-04757-3

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