DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0030
12 Molecular and Cell Biology of Autoantibodies and Autoimmunity
ject, exclude, those clones secreting antibody against nucleic acid. We are current-
ly characterising the cognate antigens of five monoclonal autoantibodies selected
in this way. They are being studied in detail using immunocytochemistry, im-
munoblotting and immunoprecipitation in different cell types and different
species. The results of these experiments will be presented. These studies indicate
that this is a productive approach for the generation of monoclonal antibodies
to physiologically interesting nuclear proteins. Knowledge of the range of nuclear
proteins that can act as autoantigens will also give some insight into the nature
of autoimmunity.
Alterations of the Macrophage System in Systemic Lupus
Erythematosus (SLE) Developing NZB/W Mice
A. Emmendbrffer, M. Muller, K. Hartung, and M.-L. Lohmann-Matthes
Dept, for Immunobiology, Fraunhofer-Institute Hannover, FRG
In SLE, a disease characterised by high titers of autoantibodies against several
autoantigens (i.e. single and double stranded DNA) and by profound disturbance
of the T- and B-celLsystem circulating immune complexes result in a servere im-
munecomplex-glomerulonephritis. Since the role of macrophages in this disease
is investigated only partially, our group examined the macrophage lineage in fe-
male SLE-developing NZB/W-F1 hybrid mice and agematched female
BALB/c-mice as controls. We examined the animals at two different stages of dis-
ease, one group at an age of 6-8 weeks with no clinical symptoms (no pro-
teinuria) and one with mice at a late stage of the disease with manifested
glomerulonephritis. We isolated macrophages and macrophage precursors from
different anatomical sites (liver, spleen and bone-marrow) and analysed their ef-
fector functions. The cytotoxic activity of the macrophages was tested against the
TNF-sensitive target cell WEHI 164 and the TNF-resistant cell P815 in a
51Chrom release assay. Microbicidal activity was investigated in a radioactivity
release assay against 3H-Thymidin prelabeled Leishmania donovani pro-
mastigotes. These protozoa are obligate intracellular parasites in macrophages. In
addition, the macrophage precursors, non-adherent, non-phagocytic and NK-ac-
tive cells were tested against the NK-target YAC 1. Further the secretion of TNF-a
IL 1 and PGE2 by organ-associated macrophages was tested.
Our rsults show an increased number of macrophages in liver and spleen and
a up to 5 fold increase of macrophage precursors in the liver of the NZB/W-mice
ject, exclude, those clones secreting antibody against nucleic acid. We are current-
ly characterising the cognate antigens of five monoclonal autoantibodies selected
in this way. They are being studied in detail using immunocytochemistry, im-
munoblotting and immunoprecipitation in different cell types and different
species. The results of these experiments will be presented. These studies indicate
that this is a productive approach for the generation of monoclonal antibodies
to physiologically interesting nuclear proteins. Knowledge of the range of nuclear
proteins that can act as autoantigens will also give some insight into the nature
of autoimmunity.
Alterations of the Macrophage System in Systemic Lupus
Erythematosus (SLE) Developing NZB/W Mice
A. Emmendbrffer, M. Muller, K. Hartung, and M.-L. Lohmann-Matthes
Dept, for Immunobiology, Fraunhofer-Institute Hannover, FRG
In SLE, a disease characterised by high titers of autoantibodies against several
autoantigens (i.e. single and double stranded DNA) and by profound disturbance
of the T- and B-celLsystem circulating immune complexes result in a servere im-
munecomplex-glomerulonephritis. Since the role of macrophages in this disease
is investigated only partially, our group examined the macrophage lineage in fe-
male SLE-developing NZB/W-F1 hybrid mice and agematched female
BALB/c-mice as controls. We examined the animals at two different stages of dis-
ease, one group at an age of 6-8 weeks with no clinical symptoms (no pro-
teinuria) and one with mice at a late stage of the disease with manifested
glomerulonephritis. We isolated macrophages and macrophage precursors from
different anatomical sites (liver, spleen and bone-marrow) and analysed their ef-
fector functions. The cytotoxic activity of the macrophages was tested against the
TNF-sensitive target cell WEHI 164 and the TNF-resistant cell P815 in a
51Chrom release assay. Microbicidal activity was investigated in a radioactivity
release assay against 3H-Thymidin prelabeled Leishmania donovani pro-
mastigotes. These protozoa are obligate intracellular parasites in macrophages. In
addition, the macrophage precursors, non-adherent, non-phagocytic and NK-ac-
tive cells were tested against the NK-target YAC 1. Further the secretion of TNF-a
IL 1 and PGE2 by organ-associated macrophages was tested.
Our rsults show an increased number of macrophages in liver and spleen and
a up to 5 fold increase of macrophage precursors in the liver of the NZB/W-mice