Abstract:
:To delineate the role of the IgH 3' enhancer in the regulation of Ig heavy (IgH) chain gene expression, mice harbouring rearranged IgH transgenes, with (PSVmu3) and without (PSVmu1) this element, were produced. RNA and protein analysis from the different transgenic lines revealed a 5- to 7-fold increase in the expression level of the transgene containing the IgH 3' enhancer. This difference is also reflected at the protein level in hybridomas generated from the two transgenic lines. The elevation of transgene Ig expression in the PSVmu3 lines is restricted to activated B lymphocytes, an observation which is further supported by the ability of this transgene to be reactivated upon immunization. Interestingly, although the up-regulation of transgene expression in PSVmu3 animals is considerably higher in comparison to the PSVmu1 animals, a significant response is still observed in the PSVmu1 mice. We speculate therefore that the IgH locus is subject to transcriptional modification in late B cell development. Our data suggest that both the Emu enhancer and the IgH 3' enhancer can up-regulate transgene Ig expression, but the presence of the 3' enhancer results in elevated levels of transgene Ig production. It therefore appears that the expression level of IgH genes is subject to transcriptional modification during B cell development. Additional control elements are most likely required for optimal Ig expression, since our expression data from the transgene in PSVmu3 animals are incompatible with endogenous Ig levels. The recent identification of additional enhancer elements in the far 3' end of the IgH locus supports this possibility. The data presented here provides a sound basis for the production of high levels of mAb, possibly tailored to suit the needs of the researcher.
journal_name
Int Immunoljournal_title
International immunologyauthors
Arulampalam V,Furebring C,Samuelsson A,Lendahl U,Borrebaeck C,Lundkvist I,Pettersson Sdoi
10.1093/intimm/8.7.1149subject
Has Abstractpub_date
1996-07-01 00:00:00pages
1149-57issue
7eissn
0953-8178issn
1460-2377journal_volume
8pub_type
杂志文章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::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::To develop a comprehensive catalogue of phenotypic and functional parameters of human CD4(+) T cell differentiation stages, we have performed microarray gene expression profiling on subpopulations of human thymocytes and circulating naive CD4(+) T cells, including CD3(-)CD4(+)CD8(-) intrathymic T progenitor cells, CD3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh112
更新日期:2004-08-01 00:00:00
abstract::The immediate responses to aerosolized staphylococcal enterotoxin B (SEB) in respiratory toxic shock were studied in the circulation of rhesus monkeys with low antibody levels following immunization with SEB toxoid-containing microspheres. Both the surviving and dying monkeys had toxic shock syndrome 4-48 h after SEB ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.12.1825
更新日期:1997-12-01 00:00:00
abstract::Natural killer (NK) cells are a major FcγRIIIA-expressing lymphocyte population that mediate antibody-dependent cellular cytotoxicity. Although NK cells are critical for immunity against viruses and tumors, they are also activated in the joints of patients with rheumatoid arthritis (RA) and may be involved in disease ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxz010
更新日期:2019-04-26 00:00:00
abstract::Man has been found to produce highly conserved chitinases. The most prominent is the phagocyte-derived chitotriosidase, the plasma levels of which are markedly elevated in some pathological conditions. Here, we report that both polymorphonuclear neutrophils (PMNs) and macrophages (m) are a source of chitotriosidase. T...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh328
更新日期:2005-11-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate m...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.2.223
更新日期:1998-02-01 00:00:00
abstract::Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive nontargeted metabolomics approach combining capillary electropho...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa059
更新日期:2020-08-31 00:00:00
abstract::Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by a murine hybridoma, was originally found to inhibit the generation of lipopolysaccharide (LPS)-induced Ig-secreting cells. Most recently, we demonstrated the recombinant form of the ubiquitin-like segment (rUbi-L) or MNSF beta, an isoform of MN...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.11.1659
更新日期:1996-11-01 00:00:00
abstract::Toll-like receptors (TLRs) recognize a variety of microbial products and induce defense responses. Pathogen sensing by TLRs occurs either on the cell surface or in endolysosomes. TLR-dependent responses are greatly influenced by the site of pathogen sensing. TLR heterodimers TLR1/TLR2 and TLR2/TLR6 recognize tri- or d...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxu054
更新日期:2014-10-01 00:00:00
abstract::Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunizat...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.8.1139
更新日期:1998-08-01 00:00:00
abstract::In this study, we analyzed peripheral blood CD4+CD8+ double-positive (DP) lymphocytes in adult cynomolgus monkeys (Macaca fascicularis). Forty of 55 monkeys had > 5% of the peripheral blood DP subpopulation (9.3 +/- 5.9%; mean +/- SD) in peripheral blood lymphocytes (PBL) in contrast to a low percentage of peripheral ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.4.591
更新日期:1997-04-01 00:00:00
abstract::The immunomodulator FTY720 inhibits lymph node (LN) and thymic egress, thereby constraining T cell circulation and reducing peripheral T cell numbers. Here, we analyzed in mouse models the as yet scarcely characterized impact of long-term (up to 6 months) FTY720 exposure on T cell homeostasis and possible consequences...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn023
更新日期:2008-05-01 00:00:00
abstract::Lymphocytes circulate in a quiescent (G(0)) state until they encounter specific antigens. In T cells, quiescence is programmed by transcription factors of the forkhead box O (FOXO) and Krüppel-like factor (KLF) families. However, the transcription factors that regulate B cell quiescence are not known. KLF4 is a candid...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn024
更新日期:2008-05-01 00:00:00
abstract::The association of celiac disease (CD) with HLA-DQ2 and HLA-DQ8 is indicative of preferential mucosal T cell recognition of gluten fragments bound to either DQ allele. We have recently identified two gluten-derived, HLA-DQ8-restricted T cell stimulatory peptides, one each from gliadin and glutenin, recognized by speci...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.8.1157
更新日期:2000-08-01 00:00:00
abstract::A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxu105
更新日期:2015-05-01 00:00:00
abstract::Pathogenic intracellular bacteria often hijack macrophages for their propagation. The infected macrophages release IL-1β and IL-18 and simultaneously commit suicide, which is called pyroptosis; both responses require caspase-1. Here, we found that pyroptotic cells induced by microbial infection were efficiently engulf...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxs161
更新日期:2013-06-01 00:00:00
abstract::Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than pare...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.10.1453
更新日期:1997-10-01 00:00:00
abstract::Protein antigens elicit humoral responses in mice that consist predominantly of IgG1 antibodies. We have now investigated the ability of IL-12, a cytokine reported to augment IgG2a anti-hapten responses through activation of Th1 cells, to alter antibody responses to hen eggwhite lysozyme (HEL). The normal response of ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.9.1519
更新日期:1995-09-01 00:00:00
abstract::Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseas...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxu086
更新日期:2015-02-01 00:00:00
abstract::Naive and primed alpha beta T cells can be distinguished on the basis of their differential expression of CD45RA and CD45RO, respectively. The present study indicates that these CD45-isoforms also identify naive and primed maturational stages of gamma delta T cells and natural killer (NK) cells. In peripheral blood, a...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.7.691
更新日期:1991-07-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.5.435
更新日期:1991-05-01 00:00:00
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 ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq042
更新日期:2010-07-01 00:00:00
abstract::CD100/Sema4D belongs to the semaphorin family, factors known to act as repulsive cues for axons during neuronal development. Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72. It remains controversial, however, whether human CD100 can function thro...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg098
更新日期:2003-08-01 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
abstract::B cell development is a complex process involving interactions between B cell precursors, stroma, and known and unknown ligands and cytokines. In order to more fully understand the requirements for Ig in that development we have created transgenic mice that carry a gamma 2b transgene and express it early in B cell dev...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.3.415
更新日期:1997-03-01 00:00:00
abstract::CD18-deficient PL/J mice develop dermatitis characterized by hyperkeratosis, and a mixed dermal and epidermal inflammatory infiltrate. The development of this disease requires low-level CD18 expression and at least two PL/J loci. Currently, the mechanisms by which decreased beta(2) integrin expression on leukocytes pr...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh028
更新日期:2004-02-01 00:00:00
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journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq434
更新日期:2010-10-01 00:00:00
abstract::Naive CD4(+) T cells rapidly proliferate to generate effector cells after encountering an antigen and small numbers survive as memory T cells in preparation for future immunological events. In the present work, adoptive transfer of naive CD4(+) T cells into RAG2(-/-) mice caused the generation of memory-type effector ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm114
更新日期:2007-12-01 00:00:00
abstract::O-acetyl GD3 ganglioside is a cell surface molecule of some neural, neural crest and renal cells. Here we show, by using mAbs specific for O-acetyl GD3 (clone 27A) and flow-cytometric, biochemical or immunological techniques, that it is also expressed at high intensity level on the surface of 49.6% (median) of the CD3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.9.1409
更新日期:1994-09-01 00:00:00