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

Cell Immunol. 2006 Jun;241(2):85-94. doi: 10.1016/j.cellimm.2006.08.002. Epub 2006 Sep 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Autoantibodies / immunology
  • B-Cell Activation Factor Receptor / metabolism*
  • B-Lymphocytes / cytology
  • Germinal Center / immunology
  • Hyperplasia / immunology
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Intestine, Small / cytology
  • Intestine, Small / pathology*
  • Kidney / cytology
  • Kidney / immunology*
  • Kidney / pathology
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mucous Membrane / cytology
  • Mucous Membrane / pathology*
  • Phenotype
  • Signal Transduction
  • Syndrome
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / deficiency
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism*

Substances

  • Autoantibodies
  • B-Cell Activation Factor Receptor
  • Immunoglobulin A
  • Lymphotoxin beta Receptor
  • Tumor Necrosis Factor Ligand Superfamily Member 14