Therefore, together with other recent studies [31, 32], these observations may help to understand why rapamycin monotherapy is not very effective in preventing graft rejection, and is sometimes even Venetoclax mouse accompanied by inflammatory side effects, including

pneumonitis and glomerulonephritis [36]. The authors would like to thank Dr Gwenny M. Fuhler for advice on immunoblotting. The authors declare no financial or commercial conflicts of interest. “
“In mice, the plasma cell (PC) niche in the bone marrow is close to the haematopoietic stem cell (HSC) niche. We investigated whether PCs can be mobilized into the peripheral blood (PB) in healthy donors receiving granulocyte colony-stimulating factor (G-CSF) for the induction of HSC mobilization into the PB.

G-CSF increased the count of circulating PCs 6-fold, that of circulating B lymphocytes 4-fold and that of circulating HSCs 44-fold. Mobilized circulating PCs comprised CD138− (62·2%) and CD138+ (37·8%) PCs, the latter being more mature based on increased CD27, CD38 and cytoplasmic immunoglobulin selleck inhibitor expression. Mobilized PCs had a phenotype close to that of steady-state PB PCs or in vitro generated PCs, but they expressed L-selectin only weakly. Finally, a median value of 0·4 × 106/kg donor PCs – one-thirtieth of the overall PC count in a healthy adult – was grafted into patients, which could contribute to immune memory recovery. After they have been generated in the lymph nodes, plasmablasts exit into the lymphatic system. They flow out into the peripheral blood (PB) via the thoracic duct and have to find a niche in the bone marrow (BM), spleen, Farnesyltransferase mucosa-associated lymphoid tissues (MALTs) or lymph nodes.1 In these niches, plasmablasts further differentiate into mature plasma cells (PCs) and may survive for decades.2 Long-term surviving PCs are responsible for the long-term humoral immune memory. Consistent with this, treatment with anti-CD20 monoclonal

antibodies (mAbs), which completely delete B cells, did not affect the levels of circulating immunoglobulins.3 The rarity of the niche supporting the long-term survival of PCs is a key factor of the regulation of humoral responses. In fact, newly generated plasmablasts have to compete with already established long-lived PCs to gain access to these rare niches.4 In mice, the PC niche has been shown to be similar to the haematopoietic stem cell (HSC) and pre-pro B-cell niche. Insertion of the green fluorescent protein (GFP) gene into the stromal cell-derived factor-1 [SDF-1 or chemokine (C-X-C motif) ligand 12 (CXCL 12)] gene made it possible to show that all murine BM PCs as well as HSCs and pre-pro B cells adhere to SDF-1+ vascular cell adhesion molecule (VCAM1)+ cells, which represent 1% of BM cells.