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...

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Bibliographic Details
Published in:Cellular Immunology 2006-06, Vol.241 (2), p.85-94
Main Authors: McCarthy, Douglas D., Chiu, Sidney, Gao, Yunfei, Summers-deLuca, Leslie E., Gommerman, Jennifer L.
Format: Article
Language:English
Subjects:
Aging - immunology
Animals
Autoantibodies - immunology
B cell
B-Cell Activation Factor Receptor - metabolism
B-Lymphocytes - cytology
BAFF
Germinal Center - immunology
Glomerulonephritis
Hyperplasia - immunology
IgA
Immunoglobulin A - blood
Immunoglobulin A - immunology
Intestine, Small - cytology
Intestine, Small - pathology
Kidney
Kidney - cytology
Kidney - immunology
Kidney - pathology
Lamina propria
LIGHT
Lymphotoxin beta Receptor - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mucous Membrane - cytology
Mucous Membrane - pathology
Nephritis
Phenotype
Signal Transduction
Syndrome
Tumor Necrosis Factor Ligand Superfamily Member 14 - deficiency
Tumor Necrosis Factor Ligand Superfamily Member 14 - metabolism
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Summary: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-β receptor (LTβR). 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.
ISSN:0008-8749
1090-2163
1365-2567
DOI:10.1016/j.cellimm.2006.08.002