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Anterior Pituitary Progenitor Cells Express Costimulatory Molecule 4Ig-B7-H3¹

Yasuhiro Nagai^*, Hisashi Aso^2,*, Hideki Ogasawara^*, Sachi Tanaka^*, Yoshikazu Taketa^*, Kouichi Watanabe^*, Shyuichi Ohwada^*, Michael T. Rose, Haruki Kitazawa and Takahiro Yamaguchi^*

^* Laboratory of Functional Morphology, Tohoku University, Sendai, Japan; Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Ceredigion, United Kingdom; and Laboratory of Animal Products Chemistry, Tohoku University, Sendai, Japan

Stem/Progenitor cells in the postnatal pituitary gland are embedded in a marginal cell layer around Rathke’s pouch. However, the nature and behavior of anterior pituitary progenitor cells remain unclear. We established bovine anterior pituitary progenitor cell line (BAPC)-1 from the anterior pituitary gland, which expressed stem/progenitor cell-related genes and several inflammatory cytokines. To characterize and localize these pituitary progenitor cells, we produced a mAb (12B mAb) against BAPC-1. The 12B mAb recognized the 4Ig-B7-H3 molecule, which is a costimulatory molecule and negative regulator in T cell activation. WC1⁺ T cells in young bovine PBMC express the 4Ig-B7-H3 molecule, but few or no 4Ig-B7-H3-immunoreactive cells are expressed in PBMC in adult cattle. The 12B-immunoreactive cells in the bovine anterior pituitary gland were localized around Rathke’s pouch and expressed IL-18 and MHC class II. However, the number of 12B-immunoreactive cells was lower in adult than in young cattle. BAPC-1 expressed IL-18 and MHC class II, and demonstrated phagocytotic activity. BAPC-1 also had the ability to promote CD25 expression in PBMC after 5 days of coculture, and blocking 4Ig-B7-H3 x 12B mAb enhanced their expression of CD25. In addition, the 12B-immunoreactive cells were observed around the pars tuberalis closely bordering the median eminence and in the blood vessels of the primary portal plexus in the anterior pituitary gland. These results suggest that an established BAPC-1 may originate from these progenitor cells, and that the progenitor cells with 4Ig-B7-H3 may play a critical role in the immunoendocrine network.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

² Address correspondence and reprint requests to Dr. Hisashi Aso, Laboratory of Functional Morphology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, 981-8555 Sendai, Japan. E-mail address: asosan{at}bios.tohoku.ac.jp

³ Abbreviations used in this paper: BAPC, bovine anterior pituitary progenitor cell line; LC-MS/MS, liquid chromatography/tandem mass spectrometry.