CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response.

To investigate the mechanism by which T regulatory (Treg) cells may control the early onset of autoimmunity, we have used an adoptive transfer model to track Treg, Th, and anti-chromatin B cell interactions in vivo. We show that anti-chromatin B cells secrete Abs by day 8 in vivo upon provision of undeviated, Th1- or Th2-type CD4+ T cell help, but this secretion is blocked by the coinjection of CD4+ CD25+ Treg cells. Although Treg cells do not interfere with the initial follicular entry or activation of Th or B cells at day 3, ICOS levels on Th cells are decreased.

The influence of effector T cells and Fas ligand on lupus-associated B cells.

Circulating autoantibodies against dsDNA and chromatin are a characteristic of systemic lupus erythematosus in humans and many mouse models of this disease. B cells expressing these autoantibodies are normally regulated in nonautoimmune-prone mice but are induced to secrete Abs following T cell help. Likewise, anti-chromatin autoantibody production is T cell-dependent in Fas/Fas ligand (FasL)-deficient (lpr/lpr or gld/gld) mice.

Univariate and bivariate variance component linkage analysis of a whole-genome scan for loci contributing to bone mineral density.

Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. The single major risk factor for osteoporosis is low bone mineral density (BMD) and strong evidence exists that genetic factors are in part responsible for an individual's BMD. A cohort of 40 multiplex Caucasian families selected through a proband with osteoporosis was genotyped for microsatellite markers spaced at an average of 10 cM, and linkage to femoral neck (FN), lumbar spine (LS) and trochanter (TR) BMD was analyzed using univariate and bivariate variance component linkage analysis.

The regulation and activation of lupus-associated B cells.

Anti-double-stranded DNA (anti-dsDNA) B cells are regulated in non-autoimmune mice. While some are deleted or undergo receptor editing, a population of anti-dsDNA (VH3H9/V lambda 1) B cells that emigrate into the periphery has also been identified. These cells have an altered phenotype relative to normal B cells in that they have a reduced lifespan, appear developmentally arrested, and localize primarily to the T/B-cell interface in the spleen.