Characterization of murine CD70 by molecular cloning and mAb

被引:95
作者
Oshima, H
Nakano, H
Nohara, C
Kobata, T
Nakajima, A
Jenkins, NA
Gilbert, DJ
Copeland, NG
Muto, T
Yagita, H
Okumura, K
机构
[1] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 113, Japan
[2] Univ Tokyo, Fac Med, Dept Surg 1, Tokyo 113, Japan
[3] Japan Sci & Technol Corp, CREST, Kawaguchi 332, Japan
[4] Nippon Med Sch, Dept Joint Dis & Rheumatism, Tokyo 113, Japan
[5] NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA
关键词
CD27; CD70; T cell co-stimulation;
D O I
10.1093/intimm/10.4.517
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD27, a member of the tumor necrosis factor (TNF) receptor family, has been implicated in T cell activation, T cell development and T-dependent antibody production by B cells. Its ligand CD70 has been identified only in humans, and, thus, physiological and pathological roles of the CD70-CD27 interaction remain to be determined in an experimental animal system, In the present study, we identified murine (m) CD70 by molecular cloning, and characterized its expression and function by generating an anti-mCD70 mAb, The mCD70 cDNA encoded a type II transmembrane glycoprotein of the TNF family, having 56.5% identity to the human CD70 amino acid sequence, The mCd70 gene was assigned in the central region of chromosome 17, To explore the expression and function of mCD70, we generated cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein (mCD27-lg) to mCD70 transfectants. FR70, as well as mCD27-lg, immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70 far more efficiently than mCD27-lg, FR70 also abrogated the CD28-independent co-stimulatory activity of A20 cells, The expression of mCD70 was detected on splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti-IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced mCD70 expression on splenic B cells. These results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system, FR70 will be useful for further investigating the physiological and pathological roles of the CD70-CD27 interaction in T cell development, T-dependent antibody production and various disease models in the murine system.
引用
收藏
页码:517 / 526
页数:10
相关论文
共 46 条
[1]  
ABE R, 1995, J IMMUNOL, V154, P985
[2]  
AGEMATSU K, 1995, J IMMUNOL, V154, P3627
[3]   CD27/CD70 INTERACTION DIRECTLY DRIVES B-CELL IGG AND IGM SYNTHESIS [J].
AGEMATSU, K ;
KOBATA, T ;
YANG, FC ;
NAKAZAWA, T ;
FUKUSHIMA, K ;
KITAHARA, M ;
MORI, T ;
SUGITA, K ;
MORIMOTO, C ;
KOMIYAMA, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (10) :2825-2829
[4]   B cell subpopulations separated by CD27 and crucial collaboration of CD27(+) B cells and helper T cells in immunoglobulin production [J].
Agematsu, K ;
Nagumo, H ;
Yang, FC ;
Nakazawa, T ;
Fukushima, K ;
Ito, S ;
Sugita, K ;
Mori, T ;
Kobata, T ;
Morimoto, C ;
Komiyama, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (08) :2073-2079
[5]  
AGEMATSU K, 1994, J IMMUNOL, V153, P1421
[6]  
BIGLER RD, 1988, J IMMUNOL, V141, P21
[7]  
BOWMAN MR, 1994, J IMMUNOL, V152, P1756
[8]  
BROWN GR, 1995, J IMMUNOL, V154, P3686
[9]   LYMPHOTOXIN-BETA, A NOVEL MEMBER OF THE TNF FAMILY THAT FORMS A HETEROMERIC COMPLEX WITH LYMPHOTOXIN ON THE CELL-SURFACE [J].
BROWNING, JL ;
NGAMEK, A ;
LAWTON, P ;
DEMARINIS, J ;
TIZARD, R ;
CHOW, EPC ;
HESSION, C ;
OBRINEGRECO, B ;
FOLEY, SF ;
WARE, CF .
CELL, 1993, 72 (06) :847-856
[10]  
CAMERINI D, 1991, J IMMUNOL, V147, P3165