Alexander Scheffold — Page 2

PubMed2002

Differential surrogate light chain expression governs B-cell differentiation.

Surrogate light chain expression during B lineage differentiation was examined by using indicator fluorochrome-filled liposomes in an enhanced immunofluorescence assay. Pro-B cells bearing surrogate light chain components were found in mice, but not in humans. A limited subpopulation of relatively large pre-B cells in both species expressed pre-B cell receptors. These cells had reduced expression of the recombinase activating genes, RAG-1 and RAG-2. Their receptor-negative pre-B cell progeny were relatively small, expressed RAG-1 and RAG-2, and exhibited selective down-regulation of VpreB and lambda5 expression. Comparative analysis of the 2 pre-B cell subpopulations indicated that loss of the pre-B cell receptors from surrogate light chain gene silencing was linked with exit from the cell cycle and light chain gene rearrangement to achieve B-cell differentiation.

Animals↗

PubMed2002

Rapid glucocorticoid effects on immune cells.

Apart from their classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomically mediated effects. Three different mechanisms are currently under discussion as being responsible for these effects: (1) specific interaction with the cytosolic glucocorticoid receptor (cGCR), (2) nonspecific interactions with cellular membranes and (3) specific interactions with membrane-bound glucocorticoid receptors (mGCR). With regard to the first mechanism, there is evidence that although the binding of glucocorticoids to the cGCR-associated multi-protein complex induces the further processes of the classic path, it also leads to a rapid intracellular signalling through other components of the complex (e.g. Src). For the second mechanism, a nonspecific interactive effect with cellular membranes through the intercalation of glucocorticoid molecules is being discussed, which primarily alters cellular functions by influencing cation transport via the plasma membrane and by increasing the proton leak of the mitochondria. With regard to the third, mGCR-mediated mechanism, the first evidence has now been found to suggest a physiological expression of membrane-bound glucocorticoid receptors on human cells, whereas in humans this had previously only been demonstrated on lymphoma cells. The clinical importance and therapeutic relevance of these rapid glucocorticoid effects remains unclear at present, although effects on intracellular signalling, interferences with bioenergetically relevant cell functions and the induction of apoptosis via the mGCR are being discussed. This article gives a detailed presentation of the data available at present concerning rapid glucocorticoid effects on immune cells.

Animals↗