COMPARISON OF PATHOGENIC AND NONPATHOGENIC MURINE ANTIBODIES TO DNA - ANTIGEN-BINDING AND STRUCTURAL CHARACTERISTICS

被引:136
作者
OHNISHI, K
EBLING, FM
MITCHELL, B
SINGH, RR
HAHN, BH
TSAO, BP
机构
[1] UNIV CALIF LOS ANGELES,DEPT MED,DIV RHEUMATOL,LOS ANGELES,CA 90024
[2] UNIV KENTUCKY,DEPT PATHOL,LEXINGTON,KY 40511
关键词
GLOMERULONEPHRITIS; HEPARAN SULFATE; NUCLEOSOME; V-GENE SEQUENCE;
D O I
10.1093/intimm/6.6.817
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Three pathogenic and two non-pathogenic NZB/NZW F1 mAbs to DNA were compared. Pathogenicity was defined as the ability to induce nephritis in BALB/c mice. All mAbs were IgG2a or 2b, had high avidity for double-stranded DNA and fixed complement well. All three pathogens expressed idiotype IdGN2. Mice receiving pathogenic mAbs (compared with non-pathogenic) had more glomerular IgG deposits. The unique properties of two of the pathogens were: strong homogeneous staining of Hep-2 nuclei and the ability to bind (i) nucleosomes, (ii) histone (after mAb complexed with DNA), (iii) heparan sulfate in renal basement membranes (after complexing with DNA/histone) and (iv) nuclei in vivo. Comparison of nucleotide and amino acid sequences of the V regions of heavy and light Ig chains showed use of multiple V(H)DJ(H) and V(chi)J(chi) gene families, with representation of several anti-DNA 'families' described by others. Arginine (R) occurred in the CDR2 or CDR3 of V(H) chains in all pathogens; R was absent in the CDRs of V(H) chains of non-pathogens. Positively and negatively charged AA were more frequent in V(H) CDR of pathogens than of non-pathogens. We hypothesize that the tertiary structure of mAbs determined by V(H) CDR regions permits stronger binding to negatively charged antigens (DNA and heparan sulfate) and to positively charged molecules (histone) in pathogens compared with non-pathogens.
引用
收藏
页码:817 / 830
页数:14
相关论文
共 56 条
[1]   BINDING OF CYTOSKELETAL PROTEINS BY MONOCLONAL ANTI-DNA LUPUS AUTOANTIBODIES [J].
ANDRESCHWARTZ, J ;
DATTA, SK ;
SHOENFELD, Y ;
ISENBERG, DA ;
STOLLAR, BD ;
SCHWARTZ, RS .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1984, 31 (02) :261-271
[2]   SPONTANEOUS MURINE LUPUS-LIKE SYNDROMES - CLINICAL AND IMMUNOPATHOLOGICAL MANIFESTATIONS IN SEVERAL STRAINS [J].
ANDREWS, BS ;
EISENBERG, RA ;
THEOFILOPOULOS, AN ;
IZUI, S ;
WILSON, CB ;
MCCONAHEY, PJ ;
MURPHY, ED ;
ROTHS, JB ;
DIXON, FJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1978, 148 (05) :1198-1215
[3]  
Behar S M, 1989, Int Rev Immunol, V5, P23, DOI 10.3109/08830188909086988
[4]   SOMATIC DIVERSIFICATION OF THE S107 (T15) VH11 GERM-LINE GENE THAT ENCODES THE HEAVY-CHAIN VARIABLE REGION OF ANTIBODIES TO DOUBLE-STRANDED DNA IN (NZB X NZW)F1 MICE [J].
BEHAR, SM ;
SCHARFF, MD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (11) :3970-3974
[5]   CHARACTERIZATION OF SOMATICALLY MUTATED S107 VH11-ENCODED ANTI-DNA AUTOANTIBODIES DERIVED FROM AUTOIMMUNE (NZB X NZW)F1 MICE [J].
BEHAR, SM ;
LUSTGARTEN, DL ;
CORBET, S ;
SCHARFF, MD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (03) :731-741
[6]   THE SPONTANEOUS APOPTOTIC CELL-DEATH OF NORMAL HUMAN-LYMPHOCYTES INVITRO - THE RELEASE OF, AND IMMUNOPROLIFERATIVE RESPONSE TO, NUCLEOSOMES INVITRO [J].
BELL, DA ;
MORRISON, B .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1991, 60 (01) :13-26
[7]   IMMUNOGENIC DNA-RELATED FACTORS - NUCLEOSOMES SPONTANEOUSLY RELEASED FROM NORMAL MURINE LYMPHOID-CELLS STIMULATE PROLIFERATION AND IMMUNOGLOBULIN-SYNTHESIS OF NORMAL MOUSE LYMPHOCYTES [J].
BELL, DA ;
MORRISON, B ;
VANDENBYGAART, P .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (05) :1487-1496
[8]   DNA-BINDING TO HUMAN-LEUKOCYTES - EVIDENCE FOR A RECEPTOR-MEDIATED ASSOCIATION, INTERNALIZATION, AND DEGRADATION OF DNA [J].
BENNETT, RM ;
GABOR, GT ;
MERRITT, MM .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (06) :2182-2190
[9]   ANTI-DNA ANTIBODIES AND LUPUS NEPHRITIS - THE COMPLEXITY OF CROSS-REACTIVITY [J].
BRINKMAN, K ;
TERMAAT, R ;
BERDEN, JHM ;
SMEENK, RJT .
IMMUNOLOGY TODAY, 1990, 11 (07) :232-234
[10]   AUTOIMMUNE VH GENE FAMILY - PCR-GENERATED MURINE GERMLINE VH10 GENES [J].
CHAO, M ;
VOSS, EW .
MOLECULAR IMMUNOLOGY, 1992, 29 (03) :439-442