Kappa editing rescues autoreactive B cells destined for deletion in mice transgenic for a dual specific anti-laminin Ig.

We explored mechanisms involved in B cell self-tolerance in a double- and triple-transgenic mouse model bearing the LamH-C mu Ig H chain conventional transgene and a gene-targeted replacement for a functional V kappa 8J kappa 5 L chain gene. Whereas the H chain is known to generate anti-laminin Ig in combination with multiple L chains, the H + L Ig binds ssDNA in addition to laminin. Immune phenotyping indicates that H + L transgenic B cells are regulated by clonal deletion, receptor editing via secondary rearrangements at the nontargeted kappa allele, and anergy.

Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.

G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs).

Lipopolysaccharide up-regulates platelet-derived growth factor (PDGF) alpha-receptor expression in rat lung myofibroblasts and enhances response to all PDGF isoforms.

Differential expression of PDGF receptor alpha and beta subunits controls the response of mesenchymal cells to the three PDGF isoforms (AA, AB, and BB). Cultured rat lung myofibroblasts (RLMF) possess abundant PDGF receptor-beta (PDGF-Rbeta) and little PDGF receptor-alpha (PDGF-Ralpha). Here we show that LPS up-regulates expression of PDGF-Ralpha and increases the sensitivity of RLMF to all three PDGF isoforms.