Unique Maturation Program of the IgE Response In Vivo

Erazo, Agustin; Kutchukhidze, Nino; Leung, Monica; Christ, Ana Paula Guarnieri; Urban, Joseph F.; Lafaille, Maria A. Curotto de; Lafaille, Juan J.

doi:10.1016/j.immuni.2006.12.006

Cited by 218 publications

(294 citation statements)

References 49 publications

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“…S8 ). Th is idea is consistent with the fact that IgE + cells arising from IgG + GC B cells swift ly become PCs and that IgE + B mem cells are barely detectable in mice even aft er immunization to induce an optimal IgE response 5 .…”

Section: Discussionsupporting

confidence: 64%

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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

et al. 2011

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In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (B mem ) cells or long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new culture system in which mouse na ï ve B cells undergo massive expansion and isotype switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1 or IgM / D, but not IgE, differentiate into B mem cells in vivo after adoptive transfer and can elicit rapid immune responses with the help of cognate T cells. Secondary culture with IL-21 maintains the proliferation of the iGB cells, while shifting their in vivo developmental fate from B mem cells to LLPCs, an outcome that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this system enables in vitro manipulation of B-cell fate, into either B mem cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.

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Section: Discussionsupporting

confidence: 64%

“…Finally, GC B cells expressing a high-affi nity IgG BCR are selected and diff erentiate into B mem cells and LLPCs by largely unknown mechanisms 2 -4 . Some of IgG + GC B cells further switch their BCR to IgE, but the IgE + GC B cells are localized outside GCs and rapidly diff erentiate into plasma cells 5 .…”

mentioning

confidence: 99%

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

et al. 2011

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“…This is illustrated, for example, by the absence of sequential switching upon anti-IgD injection into mice or in the N. strongylus-induced direct switch to IgE (26,49). The efficient formation of highaffinity IgE requires an IgG1 intermediate, and IgG1 patterns of somatic hypermutation can be transferred to IgE molecules (51). Because most memory cells are of the IgG1 type, their conversion to IgE + cells in a secondary response requires class-switching.…”

Section: Discussionmentioning

confidence: 99%

Control of the STAT6–BCL6 Antagonism by SWAP-70 Determines IgE Production

Audzevich

Pearce

Breucha

et al. 2013

The Journal of Immunology

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Asthma and allergies are major health concerns in which Ig isotype E plays a pivotal role. Ag-bound IgE drives mast cells and basophils into exocytosis, thereby promoting allergic and potentially anaphylactic reactions. The importance of tightly regulated IgE production is underscored by severe immunological conditions in humans with elevated IgE levels. Cytokines direct IgH class-switching to a particular isotype by initiation of germline transcription (GLT) from isotype-specific intronic (I) promoters. The switch to IgE depends on IL-4, which stimulates GLT of the Iε promoter, but is specifically and strongly impaired in Swap-70−/− mice. Although early events in IL-4 signal transduction (i.e., activation of the JAK/STAT6 pathway) do not require SWAP-70, SWAP-70 deficiency results in impaired Iε GLT. The affinity of STAT6 to chromatin is reduced in absence of SWAP-70. Chromatin immunoprecipitation revealed that SWAP-70 binds to Iε and is required for association of STAT6 with Iε. BCL6, known to antagonize STAT6 particularly at Iε, is increased on Iε in absence of SWAP-70. Other promoters bound by BCL6 and STAT6 were found unaffected. We conclude that SWAP-70 controls IgE production through regulation of the antagonistic STAT6 and BCL6 occupancy of Iε. The identification of this mechanism opens new avenues to inhibit allergic reactions triggered by IgE.

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“…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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Unique Maturation Program of the IgE Response In Vivo

Cited by 218 publications

References 49 publications

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

Control of the STAT6–BCL6 Antagonism by SWAP-70 Determines IgE Production

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

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