BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT

• Published in: Cellular Immunology Vol. 241; no. 2; pp. 85 - 94
• Main Authors: McCarthy, Douglas D., Chiu, Sidney, Gao, Yunfei, Summers-deLuca, Leslie E., Gommerman, Jennifer L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-06-2006
• 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; Glomerulonephritis; BAFF; B cell; IgA; Nephritis; LIGHT; Lamina propria; Kidney
• ISSN: 0008-8749; 1090-2163; 1365-2567
• DOI: 10.1016/j.cellimm.2006.08.002

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.