Abstract:
:MicroRNAs 125a and 125b are predicted to be able to bind to the B lymphocyte-induced maturation protein-1 (BLIMP-1) and IFN regulatory protein-4 (IRF-4) transcription factors, which are essential for plasma cell differentiation. A computational survey of the human and mouse genomes revealed that miR-125a and miR-125b are members of a multigene family located in paralogous clusters. The miR-125a cluster on chromosome 19 in humans includes miR-99b and let-7e, whereas the miR-125b cluster on chromosome 21 includes miR-99a and miR-let-7c. Our analysis of the expression profiles for these six miRs during B lineage differentiation indicated that mature miR-125a, miR-125b, miR-99b and let-7e transcripts are preferentially expressed by the actively dividing centroblasts in germinal centers (GC). However, miR-99b and let-7e are not predicted to bind BLIMP-1 or IRF-4 transcripts, and binding to the untranslated region of BLIMP-1 and IRF-4 messenger RNAs could be confirmed only for miR-125b. When the effect of miR-125b over-expression on terminal B cell differentiation was evaluated in an LPS-responsive B cell line, the induction of BLIMP-1 expression and IgM secretion was inhibited in this model system. Furthermore, miR-125b over-expression inhibited the differentiation of primary B cells and compromised the survival of cultured myeloma cells. These findings suggest that miR-125b promotes B lymphocyte diversification in GC by inhibiting premature utilization of essential transcription factors for plasma cell differentiation.
journal_name
Int Immunoljournal_title
International immunologyauthors
Gururajan M,Haga CL,Das S,Leu CM,Hodson D,Josson S,Turner M,Cooper MDdoi
10.1093/intimm/dxq042subject
Has Abstractpub_date
2010-07-01 00:00:00pages
583-92issue
7eissn
0953-8178issn
1460-2377pii
dxq042journal_volume
22pub_type
杂志文章abstract::The TCR is responsible for the specificity of cytotoxic T lymphocytes (CTL) by recognizing peptides presented in the context of MHC. By producing recombinant soluble TCR, it is possible to study this interaction at the molecular level. We generated single-chain TCR (scTCR) from tumor infiltrating lymphocytes (TIL) and...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.745
更新日期:1999-05-01 00:00:00
abstract::Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little is known, however, as to whether MD-2 directly regulates LPS recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology of lipid IVa, an analog...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.12.1595
更新日期:2001-12-01 00:00:00
abstract::Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell-mediated, inflammatory disease with similarities to multiple sclerosis in humans. Intranasal (i.n.) administration of a myelin basic protein (MBP)-derived peptide can protect susceptible mice from EAE. The mechanisms underlying this phenomenon, however...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.10.1625
更新日期:1999-10-01 00:00:00
abstract::Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1-9 in the context of I-Au. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-alpha) mRNA and biological activity on L929 ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/2.6.539
更新日期:1990-01-01 00:00:00
abstract::SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1049
更新日期:1998-08-01 00:00:00
abstract::Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the major causes of death worldwide due to acute inflammation in the lung. AT-rich interactive domain-containing 5a (Arid5a) is an RNA-binding protein involved in inflammatory autoimmune disease through post-transcriptional control of Il6...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxx004
更新日期:2017-02-01 00:00:00
abstract::Constitutive expression of p35 and p40 IL-12 mRNA was detected in splenic macrophages isolated from aged mice. Macrophages were also implicated as the cell type responsible for the dysregulated IL-6 and tumor necrosis factor (TNF)-alpha commonly observed to be constitutively produced by lymphoid cells from aged donors...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.5.745
更新日期:1997-05-01 00:00:00
abstract::Oral administration of large doses of protein antigen generally induces a state of systemic unresponsiveness currently termed mucosally induced tolerance. In this study, we used human milk protein (HMP) without casein as a multi-protein antigen for the study of mucosally induced tolerance. The HMP utilized in this stu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.4.537
更新日期:1998-04-01 00:00:00
abstract::To investigate the involvement of retinoic acid receptor (RAR)-alpha in allograft rejection, we investigated the effect of a novel selective agonist to the receptor, ER-38925, in a mouse cardiac allograft model. Prophylactic treatment with ER-38925 inhibited the acute rejection of the mouse cardiac allograft (BALB/c -...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh066
更新日期:2004-05-01 00:00:00
abstract::Analysis of immunoglobulin expression in mice transgenic for either a kappa light chain (driven by the kappa enhancer) or lambda light chain (driven by the IgH enhancer) revealed that the transgenic light chains are expressed by the majority of B lymphocytes in the neonatal mice. However, the proportion of B cells tha...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/1.5.509
更新日期:1989-01-01 00:00:00
abstract::Auto-antibodies against heat shock proteins (HSPs) are frequently found in the sera of patients with rheumatic and other autoimmune diseases. However, it is unclear whether these auto-antibodies play a role in the pathophysiology and etiology of these diseases. We found that a murine anti-HSP60 mAb enhanced the produc...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh399
更新日期:2006-04-01 00:00:00
abstract::CD70 and CD80 are co-stimulatory molecules which belong to the tumor necrosis factor family and the B7 family respectively. When they are co-expressed by gene-modified TS/A tumor cells, they provide an efficient protective and long-lasting T-dependent antitumor response. We first showed that when CD70 and CD80 were de...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg038
更新日期:2003-03-01 00:00:00
abstract::Hepatitis C virus (HCV) has the ability to persist in the majority of infected people. Strong, multispecific and sustained T-cell response is correlated with viral clearance. The mechanisms of chronicity by HCV are unclear. HCV could restrain the immune system and establish chronic infection by modulating dendritic ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq033
更新日期:2010-06-01 00:00:00
abstract::Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The majo...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.11.1687
更新日期:1997-11-01 00:00:00
abstract::AbstractImmune homeostasis is critically regulated by the balance between activating and inhibitory receptors expressed on various immune cells such as T and B lymphocytes, and myeloid cells. The inhibitory receptors play a fundamental role in the immune checkpoint pathway, thus maintaining peripheral tolerance. We re...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxz017
更新日期:2019-05-21 00:00:00
abstract::We have previously cloned the murine homolog of cDNA for the human myelomonocytic differentiation antigen, CD14. We synthesized three hydrophilic peptides derived from the predicted amino acid sequence of murine CD14 (mCD14), designated MS7.1, MS7.2, and MS7.3, respectively, and raised antisera against them. Each anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.2.205
更新日期:1991-02-01 00:00:00
abstract::Interleukin 6 (IL-6) is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 201...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa078
更新日期:2020-12-18 00:00:00
abstract::Rheumatic fever (RF) follows a throat infection with different M-serotypes of beta-hemolytic group A streptococci (GAS) and can affect different tissues, predominantly the heart. It is thought to be an autoimmune illness. Although histological examination of affected heart shows an infiltrate consisting mainly of T ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.8.1235
更新日期:1994-08-01 00:00:00
abstract::Normal human sera contained 10-60 ng/ml of soluble membrane cofactor protein (MCP, CD46) whereas sera of > 50% of the cancer patients contained > 60 ng/ml. MCP purified by immunoaffinity chromatography from both normal and cancer patients' sera consisted of three bands of 56, 47 and 29 kDa on SDS-PAGE/immunoblotting. ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.5.727
更新日期:1995-05-01 00:00:00
abstract::Incomplete T cell antigen receptor-mediated signaling induces an unresponsive state known as anergy. Previously, we had shown that anergy can be induced in antigen-primed but not naive T cells. In this report, we found that in vitro primed T cells from IL-2R alpha-deficient mice were resistant to anergy induction in c...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh397
更新日期:2006-05-01 00:00:00
abstract::Murine complement receptor type 2 (MCR2) is homologous to human CR2, whereas murine CR1 (MCR1) is structurally and evolutionary different from human CR1. Since ligand specificities of MCR1 and MCR2 are not completely clarified, we analyzed their functional characteristics to correlate them with structural information ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/5.4.337
更新日期:1993-04-01 00:00:00
abstract::Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intrade...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.10.1441
更新日期:1998-10-01 00:00:00
abstract::Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.6.673
更新日期:1992-06-01 00:00:00
abstract::A gelatin sponge model of concomitant tumor immunity was employed in order to examine the clonality of T cells associated with progressing and rejected tumor sites. Here we show that freshly isolated T cells bearing TCR V(beta)1, CDR3 RPGTGN, J(beta)1.1 and TCR V(beta)8, CDR3 GD, J(beta)1.6 predominated progressing an...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.5.639
更新日期:2000-05-01 00:00:00
abstract::Intracellular signaling triggered by the antigen receptor of primary B-1 (CD5+ B) lymphocytes is insufficient to bring about cell cycle progression to S phase; this appears to result from a block in signal propagation prior to the activation of protein kinase C. The present studies were undertaken to evaluate specific...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.7.1011
更新日期:1994-07-01 00:00:00
abstract::The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn009
更新日期:2008-04-01 00:00:00
abstract::Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive s...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxr057
更新日期:2011-09-01 00:00:00
abstract::The lectin complement pathway is initiated by binding of mannose-binding lectin (MBL) and MBL-associated serine protease (MASP) to carbohydrates. In the human lectin pathway, MASP-1 and MASP-2 are involved in the proteolysis of C4, C2 and C3. Here we report that the human MBL-MASP complex contains a new 22 kDa protein...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.859
更新日期:1999-05-01 00:00:00
abstract::CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh367
更新日期:2006-02-01 00:00:00
abstract::Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.5.625
更新日期:2001-05-01 00:00:00