Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination

Wesemann, Duane R.; Magee, Jennifer; Boboilă, Cristian; Calado, Dinis Pedro; Gallagher, M. J.; Portuguese, Andrew J.; Manis, John P.; Zhou, Xiaolong; Recher, Mike; Rajewsky, Klaus; Notarangelo, Luigi D.; Alt, Frederick W.

doi:10.1084/jem.20111155

Cited by 97 publications

(86 citation statements)

References 66 publications

(103 reference statements)

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“…Although IgE is a class-switched Ig-isotype requiring CD40L expression by T helper cells [20], total IgE levels are relatively high in mice or humans with T helper cell defects or complex human immunodeficiencies such as Wiskott Aldrich or Omenn syndrome [7,21]. Class-switching to IgE can happen either directly or in a stepwise fashion via classswitching first to IgG1 and then to IgE [22]. Immature B cells switch preferentially from IgM directly to IgE by passing the intermediate class switch to IgG1 [22].…”

Section: Discussionmentioning

confidence: 99%

Low immunoglobulin E flags two distinct types of immune dysregulation

Elkuch

Greiff

Berger

et al. 2017

Clinical and Experimental Immunology

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1These authors contributed equally to this study. SummaryDuring the last two decades, hyper-immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a singlecentre out-patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non-IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1-4) validated that non-IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low-IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.

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Section: Discussionmentioning

confidence: 99%

Low immunoglobulin E flags two distinct types of immune dysregulation

Elkuch

Greiff

Berger

et al. 2017

Clinical and Experimental Immunology

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“…We found that the increase in IL-27 production was crucial for the development of T FH cells and T-cell help to B cells for the production of IgG and survival, which might contribute to development of long-term humoural responses to, for example, parasites such as S. mansoni and F. hepatica that express various fucose-based glycan PAMPs 26 . [4][5][6]8 . Thus, our results suggest that DC-SIGNmediated DC priming via IKKe can provide the signals for establishing long-term humoural immunity via induction of both T FH and T H 2.…”

Section: Discussionmentioning

confidence: 99%

“…T FH cells produce interleukin (IL)-21, a potent cytokine that drives antibody isotype class switch recombination and B-cell proliferation, together with other factors 2,3 . Once B cells are outside GCs, IL-4 produced by T H 2 cells induces isotype switching to immunoglobulin E (IgE) antibodies [4][5][6] , which are integral in eosinophil-mediated killing and expulsion of parasitic worms from the intestines 1,7 . Sequential switching of IgG cells to IgE is essential for the development of long-lived high-affinity IgE þ plasma cells 8 .…”

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confidence: 99%

Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

et al. 2014

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Dendritic cells (DCs) orchestrate antibody-mediated responses to combat extracellular pathogens including parasites by initiating T helper cell differentiation. Here we demonstrate that carbohydrate-specific signalling by DC-SIGN drives follicular T helper cell (T FH ) differentiation via IL-27 expression. Fucose, but not mannose, engagement of DC-SIGN results in activation of IKKe, which collaborates with type I IFNR signalling to induce formation and activation of transcription factor ISGF3. Notably, ISGF3 induces expression of IL-27 subunit p28, and subsequent IL-27 secreted by DC-SIGN-primed DCs is pivotal for the induction of Bcl-6 þ CXCR5 þ PD-1 hi Foxp1 lo T FH cells, IL-21 secretion by T FH cells and T-cell-dependent IgG production by B cells. Thus, we have identified an essential role for DC-SIGN-induced ISGF3 by fucose-based PAMPs in driving IL-27 and subsequent T FH polarization, which might be harnessed for vaccination design.

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“…Outlined here is a strategy that has been utilized to conduct CSR assays and detect true IgE-expressing B cells from mice [9][10][11] . Treatment of activated B cells with trypsin, a common lab reagent to digest protein, removes both cytophylic and membrane bound surface IgE.…”

mentioning

confidence: 99%

“…B cells can be activated for CSR in the context of total splenocytes 12 or as purified splenic B cells 11 . As noted in the protocol (step 2.3), B cell enrichment is optional, and is at the discretion of the experimenter to determine if it would beneficial.…”

mentioning

confidence: 99%

Detection of True IgE-expressing Mouse B Lineage Cells

Gallagher

Shrestha

Magee

et al. 2014

JoVE

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B lymphocyte immunoglobulin heavy chain (IgH) class switch recombination (CSR) is a process wherein initially expressed IgM switches to other IgH isotypes, such as IgA, IgE and IgG. Measurement of IgH CSR in vitro is a key method for the study of a number of biologic processes ranging from DNA recombination and repair to aspects of molecular and cellular immunology. In vitro CSR assay involves the flow cytometric measurement surface Ig expression on activated B cells. While measurement of IgA and IgG subclasses is straightforward, measurement of IgE by this method is problematic due to soluble IgE binding to FcεRII/CD23 expressed on the surface of activated B cells. Here we describe a unique procedure for accurate measurement of IgE-producing mouse B cells that have undergone CSR in culture. The method is based on trypsin-mediated cleavage of IgE-CD23 complexes on cell surfaces, allowing for detection of IgE-producing B lineage cells by cytoplasmic staining. This procedure offers a convenient solution for flow cytometric analysis of CSR to IgE. Video LinkThe video component of this article can be found at

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Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination

Abstract: To be added.

Cited by 97 publications

References 66 publications

Low immunoglobulin E flags two distinct types of immune dysregulation

Low immunoglobulin E flags two distinct types of immune dysregulation

Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

Detection of True IgE-expressing Mouse B Lineage Cells

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