共查询到20条相似文献,搜索用时 15 毫秒
1.
The surrogate light chain (SL) is composed of two polypeptides, Vpre-B and lambda5. In large pre-BII cells the SL chain associates with Ig mu heavy chain (muH) to form the pre-B cell receptor (pre-BCR). In mice there are two Vpre-B genes which are 98% identical within the coding regions. The two genes are co-expressed at the RNA level and encode functional proteins that can assemble with lambda5. However, it is not known whether both gene products serve the same function in vivo. Here we have established mice that lack the Vpre-B1 gene (VpreB1(-/-)), but still express the Vpre-B2 gene, both as RNA and protein. In Vpre-B1(-/-) mice, the bone marrow cellularity and the percentage of B220+ cells is normal. However, among the B220+ cells, the percentage of pre-BI cells is increased, and the percentage of pre-BII and immature B cells is slightly decreased, suggesting that the lack of Vpre-B1 causes a partial block at the transition from pre-BI to pre-BII cells, i.e. into the pre-BCR stage. The number of cells that produce a functional pre-BCR is thus lower, but the cells that reach this stage are normal as they can be expanded by proliferation and then differentiate into more mature cells. The spleens of Vpre-B1 homozygous mutant mice show normal numbers of B and T lymphocytes. Moreover, the Ig loci are allelicly excluded and the homozygous mutant mice respond with normal levels of antigen-specific antibodies to T-dependent antigens. These results demonstrate that VpreB2 alone is capable of supporting B lymphocyte development in the bone marrow and can give rise to immuno-competent cells in the periphery. 相似文献
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Complexity of the immunoglobulin light chain V kappa 1 gene family in the New Zealand black mouse 总被引:2,自引:0,他引:2
The immunoglobulin light chain V kappa 1 gene family is polymorphic in murine inbred strains and this family has been subdivided into five sub-groups (V kappa 1A-E). The V kappa 1A sub-group contributes to approximately 2% of the total serum immunoglobulin light chains in several mouse strains. However, it has been reported that this sub-group is absent in New Zealand Black (NZB) mouse serum. Amino acid sequencing of myeloma proteins from this inbred mouse has shown that they belong to the V kappa 1B sub-group. We report here the structure of nine functional germline genes from NZB mice that have high homologies to the V kappa 1A, V kappa 1B, V kappa 1C, and V kappa 1D sub-groups. In addition, a novel germline gene representing the prototype of a new sub-group (designated V kappa 1F) has been identified. We have isolated different V kappa 1 germline genes from a single restriction fragment length polymorphism (RFLP) fragment, as well as identical V genes from two different RFLP migrating bands. Therefore, the complexity of the genes encoding the immunoglobulin variable region cannot be determined solely by RFLP analysis. Nucleotide sequence analysis of 16 V kappa 1 genes which code for NZB autoantibodies indicate that they belong to five different V kappa 1 sub-groups with five hybridomas (31%) expressing the V kappa 1A sub-group. Comparison of the sequences of V kappa 1 genes expressed in hybridomas with corresponding germline genes show no somatic mutations. 相似文献
3.
Sanchez P Crain-Denoyelle AM Daras P Gendron MC Kanellopoulos-Langevin C 《International immunology》2000,12(10):1459-1466
The B cell receptor (BCR) has a decisive role in transducing signals required for the development of B cells and their survival in the periphery. However, the processes that initiate these signals remain unclear and concepts of constitutive and ligand-dependent signaling have been proposed. Using a mu-transgenic mouse model, we have analyzed the impact of high surface IgM expression on the composition of the splenic B cell population. kappa-deficient mice homozygous for the H3-mu transgene have B cells with a higher BCR surface density than H3 heterozygous mice. This higher BCR expression is associated with an increase in the percentage and the total number of splenic B cells. In addition, an important proportion of CD23(-)CD21(+) marginal zone (MZ) B cells can be observed in H3 homozygous mice. However, these modifications operate in the absence of impairment of the positive selection process of the H3-mu/lambda1 combination over the H3-mu/lambda2 + 3 ones. These results suggest that (i) a constitutive BCR signaling directly correlated with BCR surface density is responsible for the efficient B cell colonization of the periphery with an accumulation of B cells in the MZ and (ii) a ligand-dependent BCR signal is responsible for the clonotype composition of the mature B cell repertoire. 相似文献
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de la Hera Antonio; Marston Wendy; Aranda Crisanto; Toribio Marie-Luisa; Martinez-A. Carlos 《International immunology》1989,1(5):471-478
Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible. 相似文献
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M T Ferm K S?derstr?m S Jindal A Gr?nberg J Ivanyi R Young R Kiessling 《International immunology》1992,4(3):305-311
Both bacterial and mammalian heat shock proteins (HSP) are recognized by some T cells, and hsp60 recognition has been implicated in rheumatoid arthritis. We have developed a model to study the induction of hsp60 in human monocytic cell lines. An anti-mycobacterial hsp65 mAb (ML30), cross-reacting with human hsp60 was used to screen 21 human tumor cell lines in Western blot analysis. All T cell and B cell lymphomas constitutively expressed hsp60 protein at moderate to high levels, while little or no hsp60 protein was detected in two monocytic leukemia lines. Moderate to high levels of hsp60 mRNA and protein could be induced in the THP-I monocytic leukemia cell line by heat shock, retinoic acid, interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha treatment, the highest levels obtained with a combination of IFN-gamma/TNF-alpha. This was also seen using two rabbit anti-hsp60 antisera directed against the N-terminal or C-terminal part of the human hsp60 protein. The determinants detected by the ML30 mAb or the two rabbit anti-hsp60 antisera were not cell surface expressed, as measured with immunofluorescence (FACS) analysis on control cultured or cytokine treated cell lines. This could be a useful model for studies related to the induction of hsp60 in human cells. 相似文献
9.
IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. 总被引:9,自引:0,他引:9
T Shimada T Kawai K Takeda M Matsumoto J Inoue Y Tatsumi A Kanamaru S Akira 《International immunology》1999,11(8):1357-1362
Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264. 7. The predicted protein contains the kinase domain in its N-terminus, which shares 30% identity to that of IKK-alpha or IKK-beta. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK-alpha and IKK-beta. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-alpha, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IkappaB-alpha (preferentially Ser36), and significantly stimulated NF-kappaB activation. These results suggest that IKK-i is an inducible IkappaB kinase which may play a special role in the immune response. 相似文献
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The status of Ig loci rearrangements in single cells from different stages of B cell development 总被引:14,自引:0,他引:14
Differential expression of c-kit, CD25 (TAC), surrogate L chainand cytoplasmic µH chain, and surface expression of IgMand IgD allows the separation of B220 (CD45+)B cell subpopulations.PCR analyses with DNA of single cells developed by others andby us have been used to monitor the conformation of the Ig Hand L chain gene loci in these different B lineage subpopulations.The results of these analyses indicate that B220+/c-kit+/CD25–cells are the precursors of large B220+/CD25+/slgM– which,in turn, are the precursors of small B220+/CD25+/slgM–cells. The majority of B220+/c-kit+/CD25– cells are DHJH-rearranged,with L chain loci in germline configuration and are thus pre-BI cells. More than 90% of all large B220+/CD25+/slgM–cells have at least one H chain locus VHDHJH rearranged; halfof them have also the second locus VHDHJH rearranged and arethus large pre-B II cells. Rearrangements of at least one alleleof the kL chain loci become detectable in 65% of the small B220+/CD25+/slgM–cells, 67% of the immature B and >75% of the mature B cells.The ratio of kL to L gene rearrangements in all three subpopulationsis {small tilde}10:1, indicating that the kL/L ratio is establishedas soon as rearrangements are made. 相似文献
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Sharing of the IL-2 receptor {gamma} chain with the functional IL-9 receptor complex 总被引:14,自引:0,他引:14
Kimura Yutaka; Takeshita Toshikazu; Kondo Motonari; Ishii Naoto; Nakamura Masataka; Van Snick Jacques; Sugamura Kazuo 《International immunology》1995,7(1):115-120
The third subunit, the so-called common (c) chain, of the IL-2receptor is shared among the receptors for IL-2, IL-4, IL-7and IL-15, and dysfunction of the c chain is thought to causeX-linked severe combined immunodeficiency (XSCID) ascribed toimpairment of early T cell development. However, cytokines linkedto XSCID are as yet unidentified. A mAb specific for the c chain,TUGm2, profoundly inhibited cell proliferation in response toIL-9. Another mAb, TUGm3, immunoprecipltated [125I]IL-9 cross-linkedwith either the IL-9 receptor or the c chain. These resultsdemonstrate that the c chain is included in the functional receptorcomplex for IL-9, which was initially characterized as a T cellgrowth factor and is essential for IL-9-dependent growth signaltransductlon. 相似文献
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We constructed an expression vector encoding a truncated Ig mu chain that lacks both VH and CH1 domains (mu delta m chain) and introduced the mu delta m vector into the Ig negative Abelson pre-B cell line P17-27. The transfectants expressed a large amount of the mu delta m chain on their surface, which was not complexed with the lambda 5 and VpreB surrogate light chain molecules. While P17-27 transfected with a vector for the intact micron chain (P17-27 micron) shows V kappa rearrangements in culture, V kappa rearrangements were not detected in P17-27 mu delta m cells. When the mu delta m chains on the cell surface were crosslinked by anti-mu antibodies, V kappa gene rearrangements were induced in P17-27 mu delta m. These results strongly suggest that crosslinking of the micron-lambda 5-VpreB complex on the pre-B cell surface generates a signal that activates V kappa gene rearrangement, and that the lambda 5 and VpreB molecules are necessary for the spontaneous crosslinking of surface Ig on pre-B cells. 相似文献
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S J Pickering J M McConnell M H Johnson P R Braude 《Human reproduction (Oxford, England)》1992,7(5):630-636
Human preimplantation embryos at various stages of development have been analysed using the polymerase chain reaction to amplify a 680 base pair fragment of the beta-globin gene. Successful amplification was achieved more frequently with DNA from intact embryos containing between one and 11 cells, single cumulus cells, oocytes which had failed to fertilize and polar bodies than from single blastomeres disaggregated from intact embryos and treated in an identical manner. The distribution of nuclei demonstrated using the nuclear chromophore diamino-phenyl-indole showed considerable inter-blastomere variation; however, no clear correlation between staining pattern and successful amplification was observed. The reason for the unreliable amplification of DNA from single blastomeres is unclear but this finding has important implications for preimplantation diagnosis of genetic disease. 相似文献
17.
Yoshikawa Soichiro; Kawano Yohei; Minegishi Yoshiyuki; Karasuyama Hajime 《International immunology》2009,21(1):43-52
As many as 5–15% of B-1 cells in the peritoneal cavityof adult mice produce antibodies reactive to phosphatidylcholine(PtC) and the vast majority of them express B cell receptors(BCRs) composed of VH11-µH chains utilizing the JH1 segmentand V9-L chains. This extremely skewed repertoire of PtC-reactiveB-1 cells is traditionally attributed to the expansion of particularclones in response to self or exogenous antigens. Here, we showthat the strong bias toward the JH1 usage among VH11-µHchains is already established prior to the BCR assembly, namelyat the transition from the large to the small pre-B cell stageduring B cell ontogeny in the fetal liver. Among VH11-µHclones isolated from large pre-B cells where the JH1 skewingwas not established yet, the JH1 users showed the highest abilityto form pre-B cell receptor (pre-BCR) and to induce cellularproliferation and differentiation when expressed in fetal liverpro-B cells. Thus, the JH1 users were positively selected andamplified at the pre-BCR checkpoint. When co-expressed withV9-L chains to form BCR, the JH1 users almost exclusively conferredthe PtC reactivity on BCR even though other JH users could alsoform BCR on the cell surface. Therefore, the pre-BCR-mediatedpositive selection of the JH1 users among VH11-µH chainsappears to be beneficial to the efficient generation of innate-typePtC-reactive B cells during the fetal B cell development, evenbefore the self-renewal or the antigen-driven clonal expansionof B-1 cells takes place in the peritoneal cavity. 相似文献
18.
Activation of Vgamma9Vdelta2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication 总被引:1,自引:0,他引:1
Agrati C Alonzi T De Santis R Castilletti C Abbate I Capobianchi MR D'Offizi G Siepi F Fimia GM Tripodi M Poccia F 《International immunology》2006,18(1):11-18
Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human Vgamma9Vdelta2 T lymphocytes play a critical role in the immune response against viruses, we analyzed their antiviral functions on Huh7 hepatoma cells carrying the subgenomic HCV replicon (Rep60 cells). In a transwell culture system, Rep60 cells were co-cultured with either PBMCs or highly purified gammadelta T cells stimulated by non-peptidic antigens. Vgamma9Vdelta2 T cell activation was associated with a dramatic reduction of HCV RNA levels. Neutralizing antibodies targeting IFN-gamma revealed a critical role for this cytokine in the inhibition of HCV replication. Interestingly, drugs already in clinical use, such as Phosphostim and Zoledronate, known to activate gammadelta T cells, were shown to induce the inhibition of HCV replication mediated by Vgamma9Vdelta2 T cells of HCV patients. Our data suggest that the therapeutic activation of Vgamma9Vdelta2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1-oriented immune response in HCV-infected patients. 相似文献
19.
Tartour Eric; de la Salle Henri; de la Salle Corinne; Teillaud Christophe; Camoin Luc; Galinha Annie; Latour Sylvain; Hanau Daniel; Fridman Wolf H.; Sautes Catherine 《International immunology》1993,5(8):859-868
Low affinity FcR are a heterogeneous group of glycoproteinswhich exist in transmembrane (TM) as well as in soluble forms.Two membrane isoforms of the murine type II FcR, FcRilb1 andFc;Rilb2, have been described. They result from the translationof alternatively spliced premRNA, FcRilb2 lacking sequencesof the first intracytoplasmic domain (IC1). Soluble forms ofFcR (sFcR) have previously been shown to result from proteolysisof membrane receptors. We report here the identification, inmacrophages, of a mRNA derived from the FCRll gene by splicingexons encoding the TM and IC1 domains, i.e. corresponding toa TM-deleted FcRllb2 mRNA. A soluble protein possibly encodedby this mRNA was identified in macrophage supernatants. In accordancewith FcR nomenclature, we propose to name this new FcRll IsoformFcRllb3. It is the most abundant 8FcR present in serum, as comparedwith 8FcR resulting from cleavage of membrane FcR. 相似文献
20.
mAbs specific for mouse 5 protein were prepared by fusion ofspleen cells from a hamster Immunized with recomblnant 5 proteinsynthesized in bacteria and the mouse myeloma cell line SP2/0-Ag14.Here we report the characteristics of the antibodies producedby the FS1 hybridoma. FS1 antibody stains a variety of mousepre-B cell lines but not B cell lines or T cell lines. The stainingof the pre-B cell lines Awl and C-7 by phycoerythrin (PE)-con]ugatedFS1 (FS1 - PE) can be blocked by prelncubatlon of these cellswith unconjugated FS1 antibody or with affinity purified polyclonal5 specific Ig but not with normal hamster or mouse IgG or withaffinity purified polyclonal antl-Mb-1 Ig. From these experimentswe concluded that FS1 specifically recognizes 5 protein. Weused FS1 -PE to probe for surface (s) 5+ cells in normal BALB/cmouse bone marrow. Such cells were undetectable when total bonemarrow or FACS sorted subpopulatlons were analyzed. However,when B220plus;, CD43+, s5+ bone marrow cells were cultured for4 days on the stromal cell line FLST2 in the presence of IL-7,s5 expression became apparent. Further expansion of these cellsin IL7 alone augmented the s5 expression to readily detectablelevels. This modulation may indicate that s5 expression on normalbone marrow cells in vivo is transient and that at any givenmoment only a small fraction of bone marrow cells expresseslow levels of 5 protein on the surface. Alternatively the bindingof our FS1 mAb to the s5 molecules on normal bone marrow cellsmay be blocked by other proteins binding to the 8X5 complexin vivo and directly ex vivo. Previous analysis of surface 5associated proteins on early mouse pre-B cell lines using apolyclonal anti-5 rabbit antlserum had suggested that s5 proteinwas associated with a high molecular weight protein. Analysisof 5 and Its associated proteins on early pre-B cell lines usingour FS1 mAb confirmed our previous finding and showed that theearly 5 receptor contains at least three proteins: 5, Vpre-B,and an as yet uncharacteiized protein with a molecular weightof 130,000 designated p130. 相似文献