scholarly journals Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production.

1990 ◽  
Vol 172 (2) ◽  
pp. 463-473 ◽  
Author(s):  
J F Gauchat ◽  
D A Lebman ◽  
R L Coffman ◽  
H Gascan ◽  
J E de Vries
Keyword(s):  
T Cells ◽  
Heavy Chain ◽  
Regulatory Mechanisms ◽  
Interleukin 4 ◽  
Switch Region ◽  
Class Switching ◽  
Rna Analysis ◽  
Human B Cells ◽  
Switch Regions ◽  
Ige Synthesis

Interleukin 4 (IL-4)-induced IgE production coincides with the appearance of the 2.2-kb productive epsilon-mRNA, but is preceded by synthesis of a 1.7-kb epsilon-RNA. Analysis of cDNA copies of the 5' end of this RNA indicated that the 1.7-kb epsilon-RNA is a germline epsilon immunoglobulin heavy chain transcript with an exon mapping 5' to the switch region. Transcription through switch regions has been implicated in the control of class switching. However, IL-4 or cloned CD4+ T cells were able to induce germline epsilon transcripts without inducing IgE synthesis, for which both signals were required. These results indicate that induction of human germline epsilon-RNA does not necessarily result in IgE synthesis, and that additional regulatory mechanisms are involved in class switching.

scholarly journals Disodium cromoglycate inhibits S mu-->S epsilon deletional switch recombination and IgE synthesis in human B cells.

1994 ◽  
Vol 180 (2) ◽  
pp. 663-671 ◽  
Author(s):  
R K Loh ◽  
H H Jabara ◽  
R S Geha
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Allergic Disease ◽  
Interleukin 4 ◽  
Pokeweed Mitogen ◽  
Disodium Cromoglycate ◽  
Isotype Switching ◽  
Human B Cells ◽  
Ige Synthesis

IgE synthesis requires interleukin 4 (IL-4) and a T-B cell interaction that involves the B cell antigen CD40 and its ligand expressed on activated T cells. IL-4 induces epsilon germline transcription whereas ligation of CD40 results in deletional S mu-->S epsilon switch recombination, expression of mature epsilon transcripts, and IgE synthesis and secretion. We demonstrate that disodium cromoglycate (DSCG), a drug commonly used for the prophylactic treatment of allergic disease, inhibits T cell-driven IgE synthesis by human B cells at concentrations readily achievable in the course of inhaled therapy for asthma. Inhibition of IgE synthesis by DSCG was not the result of drug toxicity because DSCG did not affect the viability of T and B cells or their proliferation to mitogens. DSCG did not interfere with CD40 ligand expression by T cells but clearly targeted the B cells because it inhibited IgE synthesis induced by anti-CD40 and IL-4 in populations of highly purified B cells. DSCG had no effect on the induction of epsilon germline transcripts by IL-4 but strongly inhibited CD40 mediated S mu-->S epsilon deletional switch recombination in IL-4-treated B cells as assayed by nested primer PCR. The effect of DSCG was not specific for CD40-mediated induction of IgE isotype switching because DSCG inhibited IgE synthesis as well as S mu-->S epsilon deletional switch recombination induced by hydrocortisone and IL-4 in B cells. Moreover, the effect of DSCG was not specific for IgE isotype switching because DSCG inhibited the synthesis of IgG4 by B cells sorted for lack of surface expression of IgG4 and stimulated with anti-CD40 and IL-4. DSCG caused only minimal inhibition (< 15%) of spontaneous IgE synthesis by lymphocytes from patients with the hyper-IgE syndrome and did not affect pokeweed mitogen-induced IgG and IgA synthesis by lymphocytes suggesting that it has little effect on B cells that have already undergone isotype switching. These results indicate that DSCG inhibits switching to IgE in B cells and suggest a novel potential mechanism for the prevention of allergic disease by DSCG.

Membranes of activated CD4+ T cells expressing T cell receptor (TcR) αβ or TcR γδ induce IgE synthesis by human B cells in the presence of interleukin-4

1992 ◽  
Vol 22 (5) ◽  
pp. 1133-1141 ◽  
Author(s):  
Hugues Gascan ◽  
Gregorio G. Aversa ◽  
Jean-Françlois Gauchat ◽  
Peter Van Vlasselaer ◽  
Maria-Grazia Roncarolo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Human B Cells ◽  
Ige Synthesis

scholarly journals Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

1979 ◽  
Vol 150 (5) ◽  
pp. 1229-1240 ◽  
Author(s):  
M S Sy ◽  
B A Bach ◽  
A Brown ◽  
A Nisonoff ◽  
B Benacerraf ◽  
...  
Keyword(s):  
T Cells ◽  
Heavy Chain ◽  
Suppressor Cells ◽  
Significant Inhibition ◽  
Regulatory Mechanisms ◽  
Delayed Type Hypersensitivity ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Manner ◽  
Coupled Cells

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

Detection of e Class Switching and IgE Synthesis in Human B Cells

Mast Cells ◽  
2005 ◽  
pp. 319-330 ◽  
Author(s):  
Jerome Pene ◽  
Florence Guilhot ◽  
Isabelle Cognet ◽  
Paul Guglielmi ◽  
Angélique Guay-Giroux ◽  
...  
Keyword(s):  
B Cells ◽  
Class Switching ◽  
Human B Cells ◽  
Ige Synthesis

scholarly journals The role of T cells and the effect of hydrocortisone on interleukin-4-induced IgE synthesis by non-T cells

2008 ◽  
Vol 90 (2) ◽  
pp. 286-292 ◽  
Author(s):  
H. G. NÜSSLEIN ◽  
T. TRÅG ◽  
M. WINTER ◽  
A. DIETZ ◽  
J. R. KALDEN
Keyword(s):  
T Cells ◽  
Interleukin 4 ◽  
Ige Synthesis

scholarly journals Circular DNA resulting from recombination between V-(D)-J joining signals and switch repetitive sequences in mouse thymocytes.

1991 ◽  
Vol 173 (3) ◽  
pp. 743-746 ◽  
Author(s):  
D D Davis ◽  
K Yoshida ◽  
L Kingsbury ◽  
H Sakano
Keyword(s):  
Heavy Chain ◽  
Repetitive Sequence ◽  
Molecular Mechanisms ◽  
Repetitive Sequences ◽  
Immunoglobulin Heavy Chain ◽  
Switch Region ◽  
Class Switching ◽  
Circular Dna

During the course of analyzing circular DNA in mouse thymocytes, novel recombinants were identified with immunoglobulin heavy chain joining gene and switch region probes. These circles represent excision products of recombination between the heptamer-nonamer motif for V-(D)-J joining and a repetitive sequence for class switching. The molecular mechanisms that generate "hybrid circles" are discussed.

scholarly journals Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes.

1994 ◽  
Vol 179 (6) ◽  
pp. 2023-2026 ◽  
Author(s):  
S Jung ◽  
G Siebenkotten ◽  
A Radbruch
Keyword(s):  
Immunoglobulin E ◽  
Low Frequency ◽  
Switch Region ◽  
Major Fraction ◽  
Class Switching ◽  
Class Switch ◽  
Inherent Feature ◽  
Functional Implications ◽  
Switch Regions ◽  
Sequential Switching

Both, in humans and in mice, a major fraction of immunoglobulin E (IgE)-expressing B lymphocytes develops by sequential Ig class switching from IgM via IgG to IgE. This sequential class switch might have functional implications for the frequency and repertoire of IgE+ cells. Here we show that in mutant mice, in which sequential switching to IgE via IgG1 is blocked, the frequency of cells switching to IgE is not affected. Thus, sequential class switching to IgE merely reflects the simultaneous accessibility of two acceptor switch regions for switch recombination, induced by one cytokine, but with markedly distinct efficiency. Analysis of switch recombination on both IgH alleles of switched cells shows that the low frequency of switching to IgE is an inherent feature of the S epsilon switch region and its control elements.

scholarly journals Two unusual forms of human immunoglobulin E encoded by alternative RNA splicing of epsilon heavy chain membrane exons.

1992 ◽  
Vol 176 (1) ◽  
pp. 233-243 ◽  
Author(s):  
K Zhang ◽  
A Saxon ◽  
E E Max
Keyword(s):  
Heavy Chain ◽  
Rna Splicing ◽  
Genomic Sequence ◽  
Immunoglobulin E ◽  
Interleukin 4 ◽  
Reading Frame ◽  
Rna Transcripts ◽  
Human Sequence ◽  
Human B Cells ◽  
Hydrophilic Residues

We present evidence for RNA transcripts encoding two forms of human epsilon immunoglobulin (Ig) heavy chain that differ significantly from those of other isotypes. We previously demonstrated three human epsilon mRNA species, instead of the two, corresponding to membrane and secreted proteins, seen with other heavy chain transcripts. In human genomic DNA downstream of the C epsilon gene, we identified sequences homologous to the two putative murine exons M1 (encoding a hydrophobic, presumably transmembrane region) and M2 (encoding hydrophilic residues). To determine the structures of epsilon transcripts containing these sequences, we amplified epsilon-related RNAs with the reverse transcriptase polymerase chain reaction. RNA was examined from fresh human B cells stimulated to IgE production by interleukin 4 plus anti-CD40, as well as from the human IgE-producing line AF10. Instead of the single CH4-M1-M2 splice product predicted for murine membrane IgE, we found two other RNA species. One form has the structure CH4-M1'-M2, in which M1' includes the human sequence homologous to the murine M1 as well as a unique segment of 52 codons further upstream in the genomic sequence; this RNA species apparently encodes the IgE expressed on the membrane of IgE-producing lymphocytes. The other RNA has the structure CH4-M2', in which M2' is spliced in an alternative reading frame that includes an additional 109 codons downstream of the termination codon of the CH4-M1'-M2 form. Because the CH4-M2' mRNA form does not encode a hydrophobic segment, its translated product should be secreted. A secreted epsilon protein of approximately the size predicted for this form was identified by Western blotting. This novel IgE protein could play a significant and distinctive role in allergic disorders.

scholarly journals Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch

1989 ◽  
Vol 9 (5) ◽  
pp. 1850-1856
Author(s):  
W Dunnick ◽  
M Wilson ◽  
J Stavnezer
Keyword(s):  
Heavy Chain ◽  
Recombination Event ◽  
Point Mutations ◽  
Immunoglobulin M ◽  
Constant Region ◽  
Switch Region ◽  
Nucleotide Substitutions ◽  
Region Gene ◽  
Constant Region Gene ◽  
Switch Regions

The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the mu and alpha constant region coding segments. Switch recombination to IgA expression results in a recombinant mu-alpha switch region upstream of the expressed alpha constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the expected products of simple mu to alpha switches. Five members of a third set of molecular clones share the same recombination site in both the mu and the alpha switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surprisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.

scholarly journals Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

1980 ◽  
Vol 151 (4) ◽  
pp. 896-909 ◽  
Author(s):  
M S Sy ◽  
A R Brown ◽  
B Benacerraf ◽  
M I Greene
Keyword(s):  
T Cells ◽  
Intravenous Injection ◽  
Heavy Chain ◽  
Subcutaneous Administration ◽  
Regulatory Mechanisms ◽  
Delayed Type Hypersensitivity ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Effector Cells ◽  
Lymph Node Cells

Delayed-type hypersensitivity (DTH) to p-azobenzenearsonate (ABA) can be induced in A/J mice with intravenous injection of minute amounts of anti-cross-reactive idiotypic (CRI) antibodies, providing that the animals have been pretreated 2 d earlier with low doses of cyclophosphamide (50 mg/kg). However intravenous injection of the F(ab')2 fragments of the anti-CRI antibodies or subcutaneous administration with anti-CRI antibodies induces comparable immunity in both cyclophosphamide-pretreated and normal nontreated animals. Furthermore adoptive transfer experiments indicate that lymph node cells taken from animals sensitized with anti-CRI 4 d earlier can adoptively transfer immunity to naive recipients. Transfer of immunity is mediated by a population of thymus-dependent (T) cells, which express idiotypic structures on their surface. Treatment of effector cells with either anti-theta serum or anti-idiotypic antibodies plus complement completely abrogated their ability to transfer immunity. In addition idiotype-bearing suppressor T cells induced with ABA-coupled spleen cells inhibit the development of ABA-specific DTH induced with anti-CRI antibodies. Genetic analysis revealed that the ability of anti-CRI antibodies to induce ABA-specific DTH was linked to Igh-1 heavy-chain allotype. Anti-idiotypic antibodies to the major CRI associated with anti-ABA antibodies in A/J mice failed to induce significant immunity in BALB/c mice (H-2d, Igh-1a). Nevertheless, they were able to induce significant immunity in C.AL20 mice (H-2d, Igh-1d) which possess a heavy-chain allotype similar to that of A/J mice.

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