The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

He, Jiacai; Meyer‐Hermann, Michael; Xiangying, Deng; Zuan, Lim Yok; Jones, Leigh Ann; Ramakrishna, Lakshmi; Vries, Victor C. de; Dolpady, Jayashree; Hoi, Aina; Joseph, Sabrina S.; Narayanan, Sriram; Subramaniam, Sharrada; Puthia, Manoj; Wong, Glenn; Xiong, Huizhong; Poidinger, Michael; Urban, Joseph F.; Lafaille, Juan J.; Lafaille, Maria A. Curotto de

doi:10.1084/jem.20131539

Cited by 129 publications

(246 citation statements)

References 62 publications

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“…We observed a strong disadvantage of CD83 Interestingly, IgE responses were significantly increased in CD83 B-cKO animals compared with controls during an immunization with both NP-KLH and B. burgdorferi. Class switching to IgE can be direct or subsequent to IgG1 class switching, as revealed recently by IgE reporter mice (41)(42)(43). These studies showed that IgE-producing plasma cells derived from IgE + GC B cells are of a more transient nature compared with plasma cells derived from IgG1 + GC B cells and leave the GC after fewer selection rounds (41,43,44).…”

Section: Discussionmentioning

confidence: 89%

“…Class switching to IgE can be direct or subsequent to IgG1 class switching, as revealed recently by IgE reporter mice (41)(42)(43). These studies showed that IgE-producing plasma cells derived from IgE + GC B cells are of a more transient nature compared with plasma cells derived from IgG1 + GC B cells and leave the GC after fewer selection rounds (41,43,44). Thus, when GC B cells of CD83 B-cKO mice are present to a higher extent in the DZ of GCs, a result of the GC reaction could be increased differentiation of IgE + GC B cells into plasma cells, with the result of higher IgE titers.…”

Section: Discussionmentioning

confidence: 95%

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CD83 Modulates B Cell Activation and Germinal Center Responses

Krzyzak

Seitz

Urbat

et al. 2016

The Journal of Immunology

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CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83−/− mice have a strong reduction of CD4+ T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell–specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 95%

CD83 Modulates B Cell Activation and Germinal Center Responses

Krzyzak

Seitz

Urbat

et al. 2016

The Journal of 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%

“…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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“…The enhanced IgE produced from memory B cells after secondary immunization resulted in exacerbated active anaphylaxis in gp49B 2/2 mice, perhaps through its augmented deposition on mast cells. Recent reports indicated that both IgE and IgG1 memory B cells might contribute to the production of IgE in the recall response (52,53,67). Thus, negative regulation of the production of Ag-specific IgE from the memory B cell pool could prevent immediate hypersensitivity diseases such as asthma and allergy.…”

Section: Discussionmentioning

confidence: 99%

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

Fukao

Haniuda

Nojima

et al. 2014

The Journal of Immunology

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The rapid Ab responses observed after primary and secondary immunizations are mainly derived from marginal zone (MZ) and memory B cells, respectively, but it is largely unknown how these responses are negatively regulated. Several inhibitory receptors have been identified and their roles have been studied, but mainly on follicular B cells and much less so on MZ B, and never on memory B cells. gp49B is an Ig superfamily member that contains two ITIMs in its cytoplasmic tail, and it has been shown to negatively regulate mast cell, macrophage, and NK cell responses. In this study, we demonstrate that gp49B is preferentially expressed on memory and MZ B cells. We show that gp49B−/− mice produce more IgM after a primary immunization and more IgM and IgG1 after a secondary immunization than gp49B+/+ mice in T cell–dependent immune responses. Memory and MZ B cells from gp49B−/− mice also produce more Abs upon in vitro stimulation with CD40 than those from gp49B+/+ mice. The in vitro IgM production by MZ B cells from gp49B+/+, but not gp49B−/−, mice is suppressed by interaction with a putative gp49B ligand, the integrin αvβ3 heterodimer. In addition, gp49B−/− mice exhibited exaggerated IgE production in the memory recall response. These results suggest that plasma cell development from memory and MZ B cells, as well as subsequent Ab production, are suppressed via gp49B. In memory B cells, this suppression also prevents excessive IgE production, thus curtailing allergic diseases.

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The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

Abstract: Direct class switching to IgE generates IgE+ GC cells that are highly apoptotic and do not contribute to the memory compartment, while sequential switching through an IgG+ intermediate results in the generation of long-lived IgE+ plasma cells.

Cited by 129 publications

References 62 publications

CD83 Modulates B Cell Activation and Germinal Center Responses

CD83 Modulates B Cell Activation and Germinal Center Responses

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

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

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