BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT.
BAFF is a peripheral B cell survival factor and can mediate antibody (Ab) class switching. Over-expression of BAFF in mice results in B cell hyperplasia, elevated serum immunoglobulin (Ig), spontaneous germinal centre (GC) reactions and mild glomerulonephritis (GN). Here we show that, in addition to driving excessive levels of serum IgA, BAFF over-expression results in increased IgA levels within the intestinal lamina propria (LP) and deposition of IgA immune complexes in the renal glomerular mesangium. LIGHT has been previously shown to mediate a similar phenotype via signaling through the lymphotoxin-beta receptor (LTbetaR). We evaluated if LIGHT and BAFF cooperate in the etiology of a hyper-IgA syndrome in BAFF-overexpressing transgenic (BAFF-Tg) mice. We find that LIGHT-deficient BAFF-Tg mice exhibit similar levels of IgA in the serum, gut and kidney and develop nephritis to the same degree as LIGHT-sufficient BAFF-Tg mice. Therefore, in the context of BAFF over-expression, LIGHT is dispensable for the generation of a hyper-IgA syndrome accompanied by nephritis.
McCarthy
Douglas D
DD
Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.
Chiu
Sidney
S
Gao
Yunfei
Y
Summers-deLuca
Leslie E
LE
Gommerman
Jennifer L
JL
D000375:Aging / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology; D018858:Germinal Center / Q000276:immunology; D006965:Hyperplasia / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007421:Intestine, Small / Q000166:cytology / Q000473:pathology*; D007668:Kidney / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D013577:Syndrome; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000172:deficiency / Q000378:metabolism*
D001323:Autoantibodies; D053265:B-Cell Activation Factor Receptor; D007070:Immunoglobulin A; D053259:Lymphotoxin beta Receptor; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14