Bacterial lipopolysaccharide induces long-lasting IgA deficiency concurrently with features of polyclonal B cell activation in normal and in lupus-prone mice.
Polyclonal B cell activation (PBA) and autoimmune disease can be induced in immunologically normal mice, or enhanced in lupus-prone mice, by bacterial lipopolysaccharide (LPS). Because immune defects are common in autoimmune diseases and IgA deficiency is prevalent in patients with systemic lupus erythematosus, we investigated: (i) whether LPS might induce IgA deficiency in normal mice; (ii) whether IgA deficiency might be a feature in lupus-prone mice; (iii) whether, if present in lupus-prone mice, IgA deficiency could be further accentuated by LPS; and (iv) whether the effects of LPS on IgA concentrations of normal and lupus-prone mice might be reversible upon withdrawal of LPS. We injected normal (C57BL/6) and lupus-prone (NZB/W) mice with 50 micrograms of LPS from Salmonella minnesota Re595 twice a week for 5 weeks and then discontinued LPS for 6 weeks. We determined the concentrations of plasma immunoglobulins, DNA antibodies, and circulating immune complexes before, during, and after mice were exposed to LPS. Our results indicate that: (i) LPS induces IgA deficiency in normal mice concurrently with PBA; (ii) IgA deficiency is a feature of lupus-prone mice; (iii) LPS accentuates naturally occurring PBA and IgA deficiency in lupus-prone mice; and (iv) LPS induced, or LPS enhanced, IgA deficiency and PBA in normal and lupus-prone mice persist long after withdrawal of LPS. Thus, LPS triggers or enhances autoimmune disease by a mechanism that involves in part PBA with selective increase (IgG, IgM) and concurrent decrease (IgA) of specific isotypes.
Cavallo
T
T
Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912.
Granholm
N A
NA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004406:Dysgammaglobulinemia; D017098:IgA Deficiency; D007136:Immunoglobulins / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D011863:Radioimmunoassay; D012475:Salmonella
D000936:Antigen-Antibody Complex; D007136:Immunoglobulins; D008070:Lipopolysaccharides