Disease relevance of Lbw2

• The Sbw2 locus mapped to the identical region as Lbw2, a locus on chromosome 4 linked to glomerulonephritis and mortality, suggesting a single locus with pleiotropic effects [1].
• The New Zealand Black (NZB) Lbw2 locus (lupus NZB x New Zealand White (NZW) 2 locus) was previously linked to mortality and glomerulonephritis, but not to IgG autoantibodies, suggesting that it played a role in a later disease stage [2].

High impact information on Lbw2

• Lack of the NZB Lbw2 indeed reduced mortality and glomerulonephritis, but not serum levels of total and anti-DNA IgG Abs [2].
• These findings establish the importance of Lbw2 in the BWF1 hybrid and indicate that Lbw2, by enhancing B cell hyperactivity, promotes the early polyclonal activation of B cells and subsequent production of autoantibodies [2].
• Analysis of NZB x SNF1 backcross mice has recently revealed the existence of four dominant SWR loci (H2 on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility [3].

Biological context of Lbw2

• Because no known genes associated with B cell activation and lupus are in this interval, Lbw2 probably represents a novel B cell activation gene [2].

References