B cells differentiate in human thymus and express AIRE

Gies, Vincent; Guffroy, Aurélien; Danion, François; Billaud, Philippe; Keime, Céline; Fauny, Jean-Daniel; Susini, Sandrine; Soley, Anne; Martin, Thierry; Pasquali, Jean‐Louis; Gros, Frédéric; André-Schmutz, Isabelle; Soulas-Sprauel, Pauline; Korganow, Anne‐Sophie

doi:10.1016/j.jaci.2016.09.044

Cited by 33 publications

(40 citation statements)

References 42 publications

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“…In the human thymus AIRE is almost exclusively expressed in thymic epithelial cells (TECs): only a small fraction of thymic B cells, around 5%, express AIRE and B cells constitute just 1% of thymic lymphocytes 30 . Therefore, regarding AIRE expression there is no artifact in our data caused by thymocyte background.…”

Section: Resultsmentioning

confidence: 99%

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

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Bertonha

et al. 2018

Sci Rep

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AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such differences were not detected in the thymic tissue of infants aged 7–18 months, i.e. the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six months of life.

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Section: Resultsmentioning

confidence: 99%

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

Moreira-Filho

Bando

Bertonha

et al. 2018

Sci Rep

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“…In addition, B cells that differentiate within the thymus express Aire and APECED patients present an altered B‐cell phenotype and dysregulation in B‐cell function with B‐cell reactivity to a unique set of approximately 100 self‐proteins and production of neutralizing autoantibodies against specific cytokines …”

Section: Association Between Aire Gene Mutations With Loss Of Self‐tomentioning

confidence: 99%

Update on Aire and thymic negative selection

et al. 2017

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SummaryTwenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, and was cloned and sequenced. Its importance goes beyond its abstract link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self-non-self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene. Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens (PTAs), mTEC-thymocyte adhesion and the expression of microRNAs, among other functions. With Aire, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of PTAs, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological -i.e. it is related to self-representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of Aire as a transcriptional and post-transcriptional controller of PTAs in mTECs, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases.

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“…Cependant, il est également connu depuis plus de 30 ans que le thymus abrite aussi des lymphocytes B (LB) : ils ont été décrits pour la première fois en histologie par Isaacson et al comme des cellules rares (moins de 1 % des lymphocytes thymiques) correspondant à un groupe morphologiquement hétérogène de cellules rondes ou « astéroïdes » [1]. Jusqu'à ces 10 dernières années, leur présence a de maturer et de proliférer in situ [6,7,10,13]. La fréquence plus élevée de cellules pro-B 5 et pré-B dans le thymus, par rapport au sang périphérique [6], suggère que le microenvironnement thymique, murin et humain, supporte aussi bien la maturation complète des LT que celle des LB (Figure 2).…”

Section: Développement Des Lymphocytes B Thymiquesunclassified

“…Jusqu'à ces 10 dernières années, leur présence a de maturer et de proliférer in situ [6,7,10,13]. La fréquence plus élevée de cellules pro-B 5 et pré-B dans le thymus, par rapport au sang périphérique [6], suggère que le microenvironnement thymique, murin et humain, supporte aussi bien la maturation complète des LT que celle des LB (Figure 2). Cependant, dans le thymus, la lymphopoïèse B reste minimale, impliquant l'existence de mécanismes qui limitent la maturation B intrathymique.…”

Section: Développement Des Lymphocytes B Thymiquesunclassified

Les lymphocytes B thymiques : plus que de simples spectateurs de la lymphopoïèse T

2017

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The thymus is the central site for the differentiation and selection of T cells. It has been known for decades that B lymphocytes reside in the thymus, but little attention has been paid to this unique population. Thymic B cells are mainly located in the medulla and at the cortico-medullary junction. They develop intrathymically, do not recirculate and harbor a distinct phenotype in comparison to peripheral B cells. Furthermore, because of their activated phenotype and their precise histological localization, they have been suspected to play a role in the selection of self-reactive T cells. But it is only during this last decade that murine and human studies have highlighted their functions, such as antigen-presenting cells shaping the T cell repertoire. These works have demonstrated the major role of thymic B cells in the immune system.

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B cells differentiate in human thymus and express AIRE

Cited by 33 publications

References 42 publications

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

Update on Aire and thymic negative selection

Les lymphocytes B thymiques : plus que de simples spectateurs de la lymphopoïèse T

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B cells differentiate in human thymus and express AIRE

Cited by 33 publications

References 42 publications

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

Minipuberty and Sexual Dimorphism in the Infant Human Thymus

Update on Aire and thymic negative selection

Les lymphocytes B thymiques : plus que de simples spectateurs de la lymphopoïèse T

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Product

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Les lymphocytes B thymiques : plus que de simples spectateurs de la lymphopoïèse T