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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured the concentration of mRNAs coding for immunoglobulins, k and lambda type light chains and gamma 1 type heavy chain, in mouse spleen cells activated by bacterial lipopolysaccharide or sheep red blood cells. These mRNAs were quantitated by hybridization to radioactive DNA complementary to highly purified immunoglobulin mRNAs from mouse myelomas. In the lipopolysaccharide-stimulated spleen cells, only light chain mRNA accumulated, whereas gamma 1 type heavy chain mRNA remained unvaried. The light chain mRNA concentration also increased in purified bone-marrow-derived lymphocytes. The lipopolysaccharide-induced light chain mRNA was similar to light chain mRNAs purified from myelomas. The accumulation and disappearance of light chain mRNA in bone-marrow-derived lymphocytes coincide with the kinetics of synthesis of immunoglobulin M which is the major species induced by lipopolysaccharide. In sheep red blood cell stimulated spleen, the specific accumulation of k type light chain and gamma 1 type heavy chain mRNAs parallels immunoglobulin G synthesis. These results seem to indicate that the increment of immunoglobulin mRNA concentration in bone-marrow-derived lymphocytes is important for induction of immunoglobulin synthesis.
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PMID:Accumulation of immunoglobulin messenger ribonucleic acid in immunized mouse spleen. 33 30

This paper relates the synthesis of DNA, immunoglobulin and heavy chain (H) mRNA in murine spleen cells following activation of B cells with lipopolysaccharide from E. coli (LPS). Spleen cells (CBA/H mice) were cultivated with 10% FCS and 10 mug LPS/ml. 4 h pulses with [3H]thymidine showed that DNA synthesis was stimulated within the first day following LPS activation and exhibited a sharp peak at 24 h. The shape of the DNA synthesis curve suggests that the cells susceptible to LPS stimulation are activated in a synchronous manner. Stimulation of H-chain mRNA (H-mRNA) synthesis proceeded rapidly (within 6 h of LPS addition) and peaked around 24 h, in parallel to DNA synthesis. The H-mRNA was isolated and quantitated by making use of its interaction with IgG[1, 2]. The actual level of H-mRNA in the culture increased threefold during the first 24 h and then doubled within the next 48 h. Estimates of the actual number of H-mRNA were approximately 200 molecules H-m-RNA/cell on day 0 rising to 1800/cell on day 3. In such a mixed cell population these figures will be accurate only within a factor of 2-3 (at least 35% B cells in spleen cell suspensions at the commencement of the culture, with up to 35-60% of plasma blasts by day 3 and 4 of LPS treatment). Translation of the lymphoid cell mRNA in oocytes from Xenopus laevis demonstrated that stimulation of H-mRNA synthesis was restricted to mu-mRNA, although some gamma-mRNA was present in the original spleen cells. High levels of synthesis of immunoglobulin followed after a lag period of about 24 h following LPS addition peaking after 48 and 72 h; the proportional Ig production relative to total protein synthesis reached 26% on days 3 and 4. Stimulation of Ig production was limited to IgM. Rapid stimulation of mitosis and H-mRNA synthesis thus precedes the maximum synthesis of Ig molecules, suggesting a translational block on H-mRNA during cell maturation. There was no apparent block on the transport of H-mRNA from the nucleus during early stages of activation.
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PMID:Immunoglobulin heavy chain mRNA in mitogen-stimulated B cells. 82 29

The mechanism was investigated underlying the activity of bacterial lipopolysaccharide (LPS) as an adjuvant of antibody formation as assessed by its capacity to modulate the induction of tolerance in mice to the antigen human Ig G (HGG) into a state of immunity to HGG. The adjuvant activity of LPS was found to be closely correlated with its ability to function as a B-cell mitogen. This correlation was revealed by an analysis of the genetic control of the mitogenic and adjuvant properties of LPS utilizing the refractory state inherent in the C3H/HeJ mouse strain to these activities of LPS. Thus, mice that were the progeny of a backcross between the nonresponder C3H/JeJ parent and the responder (C3H/HeJ X CWB) F1 hybrid were individually typed for responsiveness to LPS, as an adjuvant and as a B-cell mitogen. It was found that LPS interfered with tolerance induction to HGG in vivo only in those backcross progeny whose spleen cells were also capable of responding mitogenically to LPS in vitro, demonstrating that the adjuvant and B-cell mitogenic properties of LPS are genetically linked. In contrast, these properties were observed to segregate independently from either H-2 or heavy chain allotype loci, and were not sex linked. These results are compatible with the concepts that, in this system, (a) the cellular site of action of LPS as an adjuvant is confined to B cells, and (b) the subcellular mode of action of LPS as an adjuvant may involve the delivery of a "signal" to B cells which is a stimulus for mitogenesis.
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PMID:Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS. 124 16

Seventeen murine monoclonal antibodies (mAbs) against horseshoe crab clotting factor, factor C, were prepared and characterized. When the binding sites of these mAbs were analyzed by immunoblotting, ten mAbs recognized nonreduced factor C, five mAbs were directed against the heavy chain, and two mAbs were directed against the B chain. Three mAbs, 1H4, 2C12, and 2A7, one selected from each group, were used for further study. The mAb 1H4, which recognized only nonreduced factor C molecule, inhibited the factor C activity in a dose-dependent manner. It also inhibited lipopolysaccharide (LPS)- and alpha-chymotrypsin-mediated activations of the zymogen factor C, suggesting that 1H4 binds close to the active site and/or the substrate-binding site located in the serine protease domain (B chain) of factor C. On the other hand, 2C12 and 2A7 recognized, respectively, an epitope located in the heavy and the B chains, and inhibited LPS-mediated activation of factor C, but not alpha-chymotrypsin-mediated activation of factor C or factor C activity. Both F(ab')2 and Fab' fragments derived from 2C12 inhibited LPS-mediated activation in the same manner. These three mAbs did not bind with LPS, although a factor C-mAb complex was able to bind LPS, suggesting that the LPS-mediated activation of the zymogen factor C was induced through intermolecular interaction between the LPS-bound factor C molecules. The dissociation constants (Kd) for 1H4, 2C12, and 2A7 binding to factor C were determined as 1.9 x 10(-9), 0.6 x 10(-10), and 1.8 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preparation and properties of monoclonal antibodies against lipopolysaccharide-sensitive serine protease zymogen, factor C, from horseshoe crab (Tachypleus tridentatus) hemocytes. 128 92

Lymphokine directed isotype switching is preceded by the induced expression of the corresponding germline Ig heavy chain constant region (CH) gene. This association favors a model in which lymphokine induced germline CH gene expression promotes switch recombination by increasing the accessibility of the switch region to a recombinase(s). An important prediction of this model is that the induction of germline CH RNAs represents increased specific de novo transcription. To test if this prediction is fulfilled by the switch commitment factors, IL-4 and transforming growth factor-beta (TGF-beta), we have utilized a B cell line, 1.29, that switches from IgM to IgE and IgA in vitro. In this cell line, IL-4 and TGF-beta increase germline C epsilon and C alpha RNA levels respectively, predominantly by elevating transcription of these genes. Transcription of germline C epsilon and C alpha genes appears to be independently regulated and is not affected by lipopolysaccharide or IL-5. These results are discussed in the context of the molecular events necessary to commit a B cell to an isotype switch.
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PMID:Transcriptional regulation of the germline immunoglobulin C alpha and C epsilon genes: implications for commitment to an isotype switch. 136 52

Previous results showed a developmentally regulated, strong linkage between demethylation and transcriptional activity for the light chain kappa locus in the mouse (Kelley et al., Molec. cell. Biol. 8, 930-937, 1988). These results indicate the existence of a stage of development of the B cell in which permanent expression (which may be enhancer independent) of a gene is associated with its demethylation. According to this result, demethylation could mirror terminal differentiation of a cell. We tested this hypothesis by analyzing the methylation status of immunoglobulin (Ig) genes in normal B cells before and after their activation with lipopolysaccharide (LPS) to induce IgM secretion and an immunoglobulin class switch. This pattern of methylation has been compared with that of Ig genes in nonlymphoid tissues and in transformed cell lines. In general, transformed cells are terminally differentiated cells. Our results show, that in normal splenic B cells only regions proximal to the heavy chain enhancer are demethylated. The coding regions of the c mu, c delta and the c gamma 1 genes remain methylated regardless of transcription. Demethylation of the coding regions is only detectable in transformed cell lines. Hence demethylation of immunoglobulin genes may reflect a stage of terminal differentiation in which the transcription pattern of the cell is fixed. Methylation of the genes before terminal differentiation may be necessary to allow controlled expression of genes on the transcriptional level, such as by splicing and differential termination.
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PMID:Demethylation of the constant region genes of immunoglobulins reflects the differentiation state of the B cell. 137 79

Nonautoimmune mice transgenic for the heavy chain of an IgG2b anti-double-stranded-DNA antibody express the transgene in lymphoid organs and display partial allelic exclusion of this gamma 2b transgene. The spleens of these mice are characterized by marked B-cell depletion. Although there are B cells in these mice that express the transgene and recognize double-stranded DNA, they are anergic in vivo. Recovery from the state of anergy occurs in vitro after lipopolysaccharide stimulation. Thus this transgenic model demonstrates the induction of self tolerance to an IgG autoantibody.
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PMID:Induction of tolerance to an IgG autoantibody. 151 67

We examined the effects of bacterial lipopolysaccharide and several recombinant human cytokines (tumor necrosis factor alpha and granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factors) on the expression of the genes for the phagocyte cytochrome b, an essential component of the superoxide-generating oxidase. In vitro treatment with lipopolysaccharide, tumor necrosis factor alpha, or macrophage- or granulocyte-macrophage colony-stimulating factors increased the levels of transcripts for the cytochrome b heavy chain (gp91phox) 9- to 22-fold and transcripts for the light chain (p22phox) 2- to 5-fold in cultured human monocyte-derived macrophages. The same agents, except for macrophage colony-stimulating factor, induced the expression of the cytochrome b heavy chain gene 2- to 12-fold and light chain gene 2- to 6-fold in human granulocytes. The expression of the cytochrome b heavy and light chain genes was coordinated in both macrophages and neutrophils with regard to stimulus specificity and dose-response pattern. The time course for induction of the two genes was parallel in both cell types for all stimuli. The macrophage response to lipopolysaccharide occurred at least in part at the transcriptional level. These results show that a variety of physiological regulators modulate the coordinated expression of the cytochrome b genes.
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PMID:In vitro regulation of human phagocyte cytochrome b heavy and light chain gene expression by bacterial lipopolysaccharide and recombinant human cytokines. 171 8

An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma 2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the gamma 2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an I gamma 2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline gamma 2b transcript to the biological functions of the I gamma 2b antisense S-oligonucleotide is discussed.
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PMID:An antisense oligonucleotide complementary to a sequence in I gamma 2b increases gamma 2b germline transcripts, stimulates B cell DNA synthesis, and inhibits immunoglobulin secretion. 173 18

We previously documented that a single BCL1 leukemia cell can produce mu and gamma 1 immunoglobulin heavy chains with identical variable segments in an allelically excluded fashion without heavy chain constant region gene rearrangement. To understand the mechanism of dual mu/gamma 1 synthesis in BCL1 subclones, we have analyzed mature and pre-RNA at the nascent and steady-state levels. We find mu and gamma 1 sequences linked in pre-RNA. However, the primary mu and gamma 1 transcription units are about the same length (approximately 15 kilobases). Initiation of gamma 1 pre-RNA occurs upstream of C gamma 1 at sites identical to those seen in lipopolysaccharide/interleukin-4-induced normal B cells. We propose that dual mu/gamma 1 RNA synthesis occurs by a discontinuous transcription mechanism involving either trans-splicing or ligation of mu pre-RNA initiated 5' of the variable-diversity-joining region to gamma 1 pre-RNA initiated 5' of C gamma 1.
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PMID:Coexpression of mu and gamma 1 heavy chains can occur by a discontinuous transcription mechanism from the same unrearranged chromosome. 174 77


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