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Genomic Organization and Expression Analysis of B7-H4, an Immune Inhibitory Molecule of the B7 Family ¹

In-Hak Choi^2,*,, Gefeng Zhu^2,*, Gabriel L. Sica^*, Scott E. Strome, John C. Cheville, Julie S. Lau^*, Yuwen Zhu^*, Dallas B. Flies^*, Koji Tamada^* and Lieping Chen^3,*

Departments of ^* Immunology, Otorhinolaryngology, and Laboratory Medicine and Pathology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905; and Department of Microbiology, Inje University College of Medicine, Pusan, Korea

B7-H4 is a recently identified B7 family member that negatively regulates T cell immunity by the inhibition of T cell proliferation, cytokine production, and cell cycle progression. In this study, we report that the genomic DNA of human B7-H4 is mapped on chromosome 1 comprised of six exons and five introns spanning 66 kb, of which exon 6 is used for alternative splicing to generate two different transcripts. Similar B7-H4 structure is also found in mouse genomic DNA in chromosome 3. A human B7-H4 pseudogene is identified in chromosome 20p11.1 with a single exon and two stop codons in the coding region. Immunohistochemistry analysis using B7-H4-specific mAb demonstrates that B7-H4 is not expressed on the majority of normal human tissues. In contrast, up to 85% (22 of 26) of ovarian cancer and 31% (5 of 16) of lung cancer tissues constitutively express B7-H4. Our results indicate a tight regulation of B7-H4 expression in the translational level in normal peripheral tissues and a potential role of B7-H4 in the evasion of tumor immunity.

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