IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE.

Haba, Seiji; Nisonoff, Alfred

doi:10.1073/pnas.89.11.5185

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…In addition to transgenic or endogenous antigens intrathymically produced by BM-derived cells [2,[5][6][7], numerous transgenic antigens, i. e. SV40 T antigen, nuclear g -galactosidase and human hepatic C-reactive protein, under transcriptional control of tissue-specific promoters, have been reported to be ectopically produced by medullary thymic epithelium and to cause T cell unresponsiveness by thymic-clonal deletion or anergy [8][9][10]. Thymic expression of endogenous tissuespecific antigens, i. e. retinal proteins, has also been proven to correlate with resistance or weak susceptibility to induction of experimental autoimmune uveoretinitis in mice, rats and monkeys [22].…”

Section: Discussionmentioning

confidence: 99%

“…Central T cell tolerance can be achieved by uptake of tolerogen from the circulation, as demonstrated by numerous cases of clonal deletion of TCR-transgenic T cells after introduction of relevant antigens [1][2][3][4]. Local production of endogenous or transgenic tolerogen by thymic bone marrow (BM)-derived cells can also cause effective T cell unresponsiveness [2,[5][6][7]. Moreover, ectopic expression and presentation of endogenous or transgenic tissue-restricted antigens by thymic medullary epithelium have been shown to induce T cell tolerance [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Central tolerance induction in natural immunoglobulin-allotype-specific T cells

2000

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While self toleance is induced to IgGb2a in Ighb / b mice, an anti‐IgGb2a T cell activity emerges in their Igha / a congenic counterparts. This activity is revealed by postnatal transfer of Igha / a T splenocytes into Igha / b F1, in which total suppression of IgG2ab expression is established. Here, we sought to determine whether the natural T cell unresponsiveness to IgG2ab in Ighb / b mice involved a central tolerance. Based on the kinetics of postnatal thymic Cγ2ab gene expression in Ighb / b mice, we transplanted thymi from Ighb / b donors of diverse ages into tolerogen‐free Igha / a nu / nu recipients. The state of T cell tolerance or responsiveness to IgG2ab in these reconstituted nu / nu hosts was determined by monitoring the capacity of their splenocytes to induce suppression in Igha / b F1. These experiments demonstrated that: (i) in the Igha / a nu / nu recipients of adult Ighb / b thymi, 33 to 65 % T splenocytes were from nu / nu recipient origin, but these peripheral Igha / a T cells were rendered tolerant to IgG2ab during their differentiation through the adult Ighb / b thymi, (ii) circulating IgG2ab was not a prerequisite for this tolerance induction, (iii) Ighb / b thymic epithelium was unable to induce tolerance to IgG2ab and (iv) IgG2ab‐producing / presenting cells, colonizing the Ighb / b thymi, were certainly responsible of full tolerance induction to IgG2ab.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Central tolerance induction in natural immunoglobulin-allotype-specific T cells

2000

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“…A distinct property of thymic B cells is that they are the first antibody-secreting cells (ASCs) that spontaneously secrete IgG, IgA and IgE which appear early in the postnatal thymus, before to the appearance of ASCs in the spleen (64,65). In a pig model, thymic B cells are also the first to undergo Ig class-switch and secrete IgG and IgA spontaneously during the gestational period and in newborn germ-free piglets, whereas splenic B cells only secrete IgM (66)(67)(68).…”

Section: The Role Of Thymic B Cells In Central Tolerancementioning

confidence: 99%

“…One explanation for why Ig class-switch and secretion may be functionally relevant in the thymus is to establish T tolerance to immunoglobulins. In the case of IgE, Haba et al show that mice become tolerant to IgE, i.e., fail to generate anti-IgE antibodies when immunized, at postnatal day 10, which coincides with the appearance of IgE ASCs in the thymus (65). Also, during the generation of a humoral response, B cells internalize, process and present antigen-derived peptides.…”

Section: The Role Of Thymic B Cells In Central Tolerancementioning

confidence: 99%

The Multifaceted Roles of B Cells in the Thymus: From Immune Tolerance to Autoimmunity

et al. 2021

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The thymus is home to a significant number of resident B cells which possess several unique characteristics regarding their origin, phenotype and function. Evidence shows that they originate both from precursors that mature intrathymically and as the entry of recirculating mature B cells. Under steady-state conditions they exhibit hallmark signatures of activated B cells, undergo immunoglobulin class-switch, and express the Aire transcription factor. These features are imprinted within the thymus and enable B cells to act as specialized antigen-presenting cells in the thymic medulla that contribute negative selection of self-reactive T cells. Though, most studies have focused on B cells located in the medulla, a second contingent of B cells is also present in non-epithelial perivascular spaces of the thymus. This latter group of B cells, which includes memory B cells and plasma cells, is not readily detected in the thymus of infants or young mice but gradually accumulates during normal aging. Remarkably, in many autoimmune diseases the thymus suffers severe structural atrophy and infiltration of B cells in the perivascular spaces, which organize into follicles similar to those typically found in secondary lymphoid organs. This review provides an overview of the pathways involved in thymic B cell origin and presents an integrated view of both thymic medullary and perivascular B cells and their respective physiological and pathological roles in central tolerance and autoimmune diseases.

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“…Quantitative analysis of bacterial populations traditionally requires the counting of colony-forming units (CFUs). Today, such analyses can also be done by more recently developed high-throughput (HT) methods that use fluorescent labeling [1], [2] genome probing microarrays [3], or quantitative PCR [4], [5]. However, these methods have significant drawbacks.…”

Section: Introductionmentioning

confidence: 99%

Automated Counting of Colony Forming Units Using Deep Transfer Learning From a Model for Congested Scenes Analysis

et al. 2020

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Reliable quantification of cellular treatment effects in many bioassays depends on the accuracy of cell colony counting. However, colony counting processes tend to be tedious, slow, and error-prone. Thus, pursuing an effective colony counting technique is ongoing, and varies from manual approaches to partly automated and fully automated techniques. Most fully automated techniques were developed using deep learning (DL). A significant problem in applying DL to this task is the lack of sizeable collections of annotated plate images. For this reason, here we propose an application of Transfer Learning to cell colony counting that can overcome this problem by exploiting models trained for other tasks. To demonstrate this idea's feasibility, we show how a small dataset can be used to transform a DL model designed for counting objects in congested scenes into a specialized cell colony counting model and achieve better performance than existing, more widely-used models.

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IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE.

Abstract: We have shown previously that normal mice become tolerant to endogenous IgE when they are approximately 2 weeks old and that this corresponds

Cited by 11 publications

References 18 publications

Central tolerance induction in natural immunoglobulin-allotype-specific T cells

Central tolerance induction in natural immunoglobulin-allotype-specific T cells

The Multifaceted Roles of B Cells in the Thymus: From Immune Tolerance to Autoimmunity

Automated Counting of Colony Forming Units Using Deep Transfer Learning From a Model for Congested Scenes Analysis

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