The Immunoglobulin Class Switch: Beyond “Accessibility”

Snapper, Clifford M.; Marcu, Kenneth B.; Żelazowski, Piotr

doi:10.1016/s1074-7613(00)80324-6

Cited by 196 publications

(146 citation statements)

References 84 publications

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“…Thus we have demonstrated that an unidentified component apart from GL transcripts and the switch recombination machinery is necessary for switching. Similar conclusions have been obtained by Mandler et al [41] and have been further discussed in a recent review by Snapper et al [51]. Mandler et al showed that B cells stimulated with anti-IgD antibodies conjugated to dextran in combination with IL-4 produced increased levels of ␥1 transcripts, but failed to switch to IgG1 unless IL-5 was also present.…”

Section: Discussionsupporting

confidence: 79%

Characterization of CD40‐Dependent Immunoglobulin Class Switching

et al. 1999

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Ström L, Laurencikiené J, Miskiniené A, Severinson E. Characterization of CD40-Dependent Immunoglobulin Class Switching. Scand J Immunol 1999;49;523-532 Previous studies have shown that signalling via CD40 together with cytokines stimulates immunoglobulin (Ig) class switching in B cells. This process includes induction of germline (GL) transcripts and switch recombination. Using an agonistic rat anti-mouse CD40 monoclonal antibody (MoAb), we investigated the role of CD40 signalling in these molecular events. We found that stimulation of murine B cells induced high steady-state levels of germline ␥1, ␥2b and low levels of ⑀ transcripts. No detectable ␥2a or ␣RNA were found and the level of ␥3 transcripts was high both in stimulated and unstimulated cells. Although cells treated with anti-CD40 MoAb had high levels of GL ␥1 and ␥3 transcripts, we failed to detect switching to IgG1 or IgG3. However, anti-CD40 MoAb-stimulated cells increased expression of IgG2b. Interestingly, anti-CD40 plus interleukin (IL)-5 induced switching to IgG1. Previous work has demonstrated that CD40 signalling, but not lipopolysaccharide (LPS), induces the ␥1 promoter and that NF-B motifs are important. We show here that both LPS and anti-CD40 activated NF-B proteins binding to the ␥1 promoter. The bound NF-B complexes were different with regard to total concentration and subunit composition. In the light of our data, the mechanism of CD40-mediated Ig class switching is discussed.

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Section: Discussionsupporting

confidence: 79%

Characterization of CD40‐Dependent Immunoglobulin Class Switching

et al. 1999

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“…[33][34][35][36][37][38] There are strains, however, capable of promoting the synthesis of interferon ␥, 33,39-42 a cytokine supporting the production of antibodies of the IgG3 isotype. [43][44][45] The IgG3 isotype, characterizing LACDE BGAL 266-280 /PDC-E2 212-226 cross-reactive antibodies, is noted for its ability to recruit major effectors of tissue damage, such as complement and Fc receptor-bearing cytotoxic cells, [46][47][48] and may have pathogenic implications in PBC. 49 We recognize that if microbes trigger AMA production and ultimately PBC, organisms other than LACDE must be implicated, 10 because the PBC-specific Lactobacillus/ self cross-reactivity observed in the present study is limited to approximately half of the PBC patients.…”

Section: Discussionmentioning

confidence: 99%

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic†

et al. 2005

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The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2 212-226 and hsp's is a cross-reactive target. Having found that this same motif is present only in ␤-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to crossreactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL 266-280 LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57%) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12%; P < .001) had anti-BGAL 266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL 266-280 /PDC-E2 212-226 reactivity of the IgG3 isotype was found in 52 (52%) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL 266-280 /PDC-E2 212-226 reactivity was due to crossreactivity as confirmed via competition ELISA. Antibody affinity for BGAL 266-280 was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL 266-280 reduced the inhibition of enzymatic activity by 40%, while marginal effect (12%) or no effect (2%) was observed in human or ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.

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“…Since its initial discovery (Sen and Gilbert 1988), G4 DNA has been implicated in biological processes such as homologous chromosomal pairing and recombination (Dunnick et al 1993;Frantz and Gilbert 1995;Liu et al 1995). The CAGGG repeats we have described in this study bear a striking resemblance both in sequence and organization to switch recombination signals (Mills et al 1990) that have been shown to mediate genomic rearrangement events that juxtapose immunoglobulin heavy chain variable regions [V(D)J] and constant regions (Snapper et al 1997). The unusual Hoogsteen pairing potential of such guaninerich sequences has been thought to underlie this phenomenon.…”

Section: Genome Research 1053mentioning

confidence: 91%

CAGGG Repeats and the Pericentromeric Duplication of the Hominoid Genome

Eichler¹,

Archidiacono²,

Rocchi³

1999

Genome Res.

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Gene duplication is one of the primary forces of evolutionary change. We present data from three different pericentromeric regions of human chromosomes, which indicate that such regions of the genome have been sites of recent genomic duplication. This form of duplication has involved the evolutionary movement of segments of genomic material, including both intronic and exonic sequence, from diverse regions of the genome toward the pericentromeric regions. Sequence analyses of the target sites of duplication have identified a novel class of interspersed GC-rich repeats located precisely at the boundaries of duplication. Estimates of the evolutionary age of these duplications indicate that they have occurred between 10 and 25 mya. In contrast, comparative analyses confirm that the GC-rich pericentromeric repeats have existed within the pericentromeric regions of primate chromosomes before the divergence of the cercopithecoid and hominoid lineages (∼30 mya). These data provide molecular evidence for considerable interchromosomal duplication of genic segments during the evolution of the hominoid genome and strongly implicate GC-rich repeat elements as playing a direct role in the pericentromeric localization of these events Genome evolution is dependent on the processes of single-base-pair mutation and gene duplication. Duplication of a gene followed by mutation is responsible for the emergence of new genes with specialized functions in an evolving species. Two distinct molecular mechanisms of gene duplication are generally recognized. Tandem duplication of an ancestral gene, vis-à-vis processes of unequal crossover, produces a clustered family of related genes (Smith 1976). In contrast, whole-genome duplication (polyploidy) followed by chromosomal rearrangement and the re-establishment of the disomic state has been proposed as a mechanism for the interchromosomal duplication of large segments of a genome (Ohno 1970). The latter model, put forward originally by Susumu Ohno, explains observations of conserved genic synteny among nonhomologous chromosomes. Because of the genetic consequences of polyploidy, such events, although important in the early expansion of eukaryotic genomes, are rare and ancient (Ohno 1993;Wolfe and Shields 1997). Within the vertebrate lineage, for example, the last tetraploidization event leading to genome duplication is estimated to have occurred >400 mya (Lundin 1993). If polyploidy were the only model by which entire genes could be duplicated among nonhomologous chromosomes, it would then follow that interchromosomal paralogs of recent origin would be unexpected.Recent analyses of data from the Human Genome Project suggest a third form of genomic duplication, which is mechanistically distinct from polyploidy and tandem duplication models of genome evolution. Several independent reports indicate that genic segments, ranging in length from 5 kb to 30 kb, possess duplicate copies within the pericentromeric regions of human autosomes (Borden et

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The Immunoglobulin Class Switch: Beyond “Accessibility”

Cited by 196 publications

References 84 publications

Characterization of CD40‐Dependent Immunoglobulin Class Switching

Characterization of CD40‐Dependent Immunoglobulin Class Switching

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic†

CAGGG Repeats and the Pericentromeric Duplication of the Hominoid Genome

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