TY - JOUR
T1 - Nephritogenic antibodies in MRL/lpr lupus mice
T2 - molecular characteristics in pathological and genetic aspects.
AU - Itoh, J.
AU - Takahashi, S.
AU - Ono, M.
AU - Yamamoto, T.
AU - Nose, M.
AU - Kyogoku, M.
PY - 1994/5
Y1 - 1994/5
N2 - MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found that IgG3 production in this strain of mice has a critical role on the development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA levels of IgG3 correlated well with the severity of GN among the MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based on these results, we have successfully established five hybridoma clones which produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When they were injected to normal mice, four of the five clones generated cell-proliferative GN associated with the marked cellular infiltrates, while the remaining clone induced wire loop-like lesions. This result suggests that particular antibodies generated in MRL/lpr mice have a different pathogenic potency. The V-region sequence study of these nephritogenic antibodies revealed that the two types of the glomerular lesions were mediated by a different B cell precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by the expansion of clonally different B cells producing nephritogenic antibodies with a different pathogenic potency.
AB - MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found that IgG3 production in this strain of mice has a critical role on the development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA levels of IgG3 correlated well with the severity of GN among the MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based on these results, we have successfully established five hybridoma clones which produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When they were injected to normal mice, four of the five clones generated cell-proliferative GN associated with the marked cellular infiltrates, while the remaining clone induced wire loop-like lesions. This result suggests that particular antibodies generated in MRL/lpr mice have a different pathogenic potency. The V-region sequence study of these nephritogenic antibodies revealed that the two types of the glomerular lesions were mediated by a different B cell precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by the expansion of clonally different B cells producing nephritogenic antibodies with a different pathogenic potency.
UR - http://www.scopus.com/inward/record.url?scp=0028440521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028440521&partnerID=8YFLogxK
U2 - 10.1620/tjem.173.65
DO - 10.1620/tjem.173.65
M3 - Review article
C2 - 7809912
AN - SCOPUS:0028440521
VL - 173
SP - 65
EP - 74
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 1
ER -