Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity in MRL-lpr/lpr mice.
The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production.
Shirai
A
A
Section of Retroviral Immunology, Food and Drug Administration, Bethesda, MD 20892.
Aoki
I
I
Otani
M
M
Mond
J J
JJ
Klinman
D M
DM
D000367:Age Factors; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003911:Dextrans / Q000008:administration & dosage*; D005260:Female; D007072:Immunoglobulin D / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007134:Immunoglobulin Switch Region; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*
D003911:Dextrans; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M