TY - JOUR
T1 - Cloning and cDNA sequence analysis of nephritogenic monoclonal antibodies derived from an MRL/lpr lupus mouse
AU - Satoru, Takahashi
AU - Junpei, Itoh
AU - Masato, Nose
AU - Masao, Ono
AU - Tokuo, Yamamoto
AU - Masahisa, Kyogoku
N1 - Funding Information:
Acknowledgements-The authors are indebted to Drs Y. Kumagai, S. Izui, H. Nagura, T. Tachibana, S. Shibahara, T. Sasakia nd T. Azuma for helpful discussionsT. he technical help of Ms S. Terasaki, K. Funada and E. Kondoh in immunochemicals tudies,a nimal care and histopathological studies,a nd the photographicw ork of Mr A. Ohkura are also highly appreciatedW. e also thank Dr A. Telekesf or critically reviewingt he manuscript.T his work was supportedin part by grantsf rom the ResearchC ommitteesM, inistry of Welfare of Japan and the Uehara Foundation, and by the Scientific ResearchF unds of the Ministry of Education, Sciencea nd Culture of Japan.
PY - 1993/2
Y1 - 1993/2
N2 - Production of IgG3 in MRL/Mp-lpr/lpr (MRL/lpr) lupus mice is one of the major factors to develop glomerulonephritis (GN) in these mice. To examine molecular characteristics of IgG3 responsible for GN in these mice, hybridoma clones producing IgG3 antibodies were prepared from one unmanipulated MRL/lpr mouse. Two clones, 2B11.3 and 7B6.8, were nephritogenic; that is, they caused severe glomerular lesions when injected to normal mice, moreover with a different histopathological manifestation. The 2B11.3 clone generated diffuse cell-proliferative lesions, while those induced by the 7B6.8 clone resembled wire loop lesions in human lupus nephritis. The cDNA sequence analysis of 7B6.8 antibody and the other IgG3 antibody, 1G3, non-nephritogenic, revealed that the C regions of the heavy and light kappa chains were completely the same between them. Furthermore, they were identical in deduced amino acid sequences to those from non-autoimmune BALB/c mice, indicating no allelic difference of Igh-8 between these two strains. The V regions of 2B11.3 and 7B6.8 antibodies were composed of different sets of VH, D, JH, Vk and Jk. Although both of the VH belonged to the J558 family, they seemed to use a different VH germline gene. These findings suggest that GN in MRL/lpr mice is generated by the expansion of clonally different B cells producing particular antibodies possibly with a different pathogenetic potency.
AB - Production of IgG3 in MRL/Mp-lpr/lpr (MRL/lpr) lupus mice is one of the major factors to develop glomerulonephritis (GN) in these mice. To examine molecular characteristics of IgG3 responsible for GN in these mice, hybridoma clones producing IgG3 antibodies were prepared from one unmanipulated MRL/lpr mouse. Two clones, 2B11.3 and 7B6.8, were nephritogenic; that is, they caused severe glomerular lesions when injected to normal mice, moreover with a different histopathological manifestation. The 2B11.3 clone generated diffuse cell-proliferative lesions, while those induced by the 7B6.8 clone resembled wire loop lesions in human lupus nephritis. The cDNA sequence analysis of 7B6.8 antibody and the other IgG3 antibody, 1G3, non-nephritogenic, revealed that the C regions of the heavy and light kappa chains were completely the same between them. Furthermore, they were identical in deduced amino acid sequences to those from non-autoimmune BALB/c mice, indicating no allelic difference of Igh-8 between these two strains. The V regions of 2B11.3 and 7B6.8 antibodies were composed of different sets of VH, D, JH, Vk and Jk. Although both of the VH belonged to the J558 family, they seemed to use a different VH germline gene. These findings suggest that GN in MRL/lpr mice is generated by the expansion of clonally different B cells producing particular antibodies possibly with a different pathogenetic potency.
UR - http://www.scopus.com/inward/record.url?scp=0027391808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027391808&partnerID=8YFLogxK
U2 - 10.1016/0161-5890(93)90089-T
DO - 10.1016/0161-5890(93)90089-T
M3 - Article
C2 - 8429833
AN - SCOPUS:0027391808
VL - 30
SP - 177
EP - 182
JO - Immunochemistry
JF - Immunochemistry
SN - 0161-5890
IS - 2
ER -