<b>OBJECTIVEb>To investigate the expression of B lymphocyte stimulator (BlyS) and its receptors in multiple myeloma (MM) cells, and to explore the relationship between BLyS and the development of human multiple myeloma.

<b>METHODSb>Flow cytometry, RT-PCR and Western blot were used to examine the expression of BLyS and its receptors in MM (KM3 and CZ1) cells. Fluorescence immunocytochemical method and confocal laser scanning technique were applied to the localization of BLyS in KM3 cell. WST proliferation assay was used to examine the effect of BLyS on MM cells growth and survival. Linear correlation analysis was used to detect LDH and beta 2-microglobulin (beta2M) levels with BLyS protein and mRNA expressions in MM patients.

<b>RESULTSb>(1) BLyS and its receptors were expressed in MM cells. (2) BLyS protein was localized on the KM3 plasma membrane. (3) BLyS promoted survival and proliferation of MM cells. (4) MM patients had significantly higher expression levels of BLyS [77.42% (24/31)] BLyS mRNA [93.55% (29/31)], which were significantly correlated with the levels of LDH and beta 2-microglobulin (beta2M).

<b>CONCLUSIONb>BLyS and its receptors in MM cell lines and MM patient bone marrow might have a potential role in the growth and survival of malignant plasma cells.

Aged ; B-Cell Activating Factor ; genetics ; metabolism ; B-Cell Activation Factor Receptor ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; pathology ; RNA, Messenger ; genetics ; beta 2-Microglobulin ; metabolism

B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-kappaB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-kappaB inhibitors. NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-kappaB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-kappaB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-kappaB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.
Arthritis, Rheumatoid/genetics/*metabolism/pathology/physiopathology ; B-Cell Activating Factor/genetics/metabolism ; B-Cell Activation Factor Receptor/genetics/*metabolism ; B-Lymphocytes/*drug effects/immunology/metabolism/pathology ; Cell Separation ; Cells, Cultured ; Disease Progression ; Enzyme Inhibitors/pharmacology ; Flow Cytometry ; Gene Expression Regulation/immunology ; Humans ; Immunohistochemistry ; NF-kappa B/*metabolism ; Signal Transduction/immunology ; Synovial Membrane/*pathology ; T-Lymphocytes/drug effects/immunology/metabolism/pathology ; Transcriptional Activation/drug effects

<b>OBJECTIVEb>To explore the expressions of B lymphocyte activating factor (BAFF) in the serum and peripheral blood B cells (PBBCs) of BXSB lupus nephritis mice, and to investigate the efficacy of Langchuangping Granule (LG).

<b>METHODSb>Eighteen 11-week-old male BXSB lupus mice were randomly divided into three groups, i.e., the lupus control group, the hormone treatment group, and the LG treatment group, 6 in each group. Besides, another 6 C57BL/6 male mice were recruited as the normal control group. The mice were given with normal sodium (10 mL/d), methylprednisolone (at the daily dose of 5 mg/kg), LG (at the daily dose of 4 g/kg), and the normal saline (10 mL/d) respectively by gastrogavage for 4 weeks. The urine protein, ds-DNA, and body weight were determined. The serum soluble BAFF (sBAFF), the expressions and changes of BAFF-mRNA in the PBBCs were detected using ELISA and RT-PCR respectively. The activity index (AI) and 24 h urine albumin excretion quantitation of renal pathological activities were observed. The correlation between ds-DNA and sBAFF were analyzed.

<b>RESULTSb>The level of sBAFF in serum, the BAFF mRNA level in PBBCs, 24 h urinary albumin excretion, and serum ds-DNA content increased more obviously in lupus mice than in the normal mice. After being treated by methylprednisolone or LG, the sBAFF and BAFF mRNA expressions decreased more obviously than before treatment, showing statistical difference (P<0.05). But there was no statistical difference in the sBAFF level or the BAFF mRNA expression (P>0.05). There was positive correlation between sBAFF and AI (r=0.8098, P<0.01), 24 h urinary albumin excretion (r=0.8220, P<0.01), and ds-DNA (r=0.8535, P<0.01).

<b>CONCLUSIONSb>BAFF plays an important role in the occurrence and development of lupus nephritis. It can be used in monitoring the disease progress and predicting its recurrence. It is one of ideal targets for treating lupus nephritis. LG could attenuate the renal injury via suppressing BAFF level. It is worth further clinical application.

Animals ; B-Cell Activation Factor Receptor ; metabolism ; B-Lymphocytes ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Lupus Nephritis ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phytotherapy ; RNA, Messenger ; genetics