TSPAN33 is a novel marker of activated and malignant B cells

Luu, Van Phi; Hevezi, Peter; Vences-Catalán, Felipe; Maravillas-Montero, José Luis; White, Clayton A.; Casali, Paolo; Llórente, Luis; Jakez‐Ocampo, Juan; Lima, Guadalupe; Vilches-Cisneros, Natalia; Flores‐Gutiérrez, Juan Pablo; Santos-Argumedo, Leopoldo; Zlotnik, Albert

doi:10.1016/j.clim.2013.08.005

Cited by 24 publications

(32 citation statements)

References 69 publications

(83 reference statements)

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“…The latter observation suggests that IL-40 may play a role in the pathogenesis of human lymphomas (42). Interestingly, the Il40 + lymphomas also express the B cell activation Ag TSPAN33 (8), indicating that they exhibit an “activated” B cell phenotype (42). Taken together, we conclude that C17orf99 encodes a novel B cell–derived cytokine (IL-40) that has significant effects in IgA production, B cell homeostasis, and, likely, B cell development.…”

Section: Resultsmentioning

confidence: 99%

“…For most of these, there is no information linking them with the immune system. We have reported three of these genes: Isthmin 1, a large secreted protein originally described in the brain of Xenopus , but which is expressed by NK, NKT, and Th17 cells in mammals (7); TSPAN33, a membrane protein that represents a novel biomarker of activated B cells (8); and Meteorin-like (6), a secreted small protein related to a known neurotrophic growth factor (meteorin) that is expressed by activated macrophages. In the current study, we focused on C17orf99 , because it is predicted to encode a small secreted protein (~27 kDa) and is expressed by activated B cells, fetal liver, and BM.…”

Section: Discussionmentioning

confidence: 99%

“…These analyses led to the identification of 35 poorly characterized genes predicted to encode transmembrane or secreted proteins expressed by leukocytes or immune system–associated organs. We have reported three of these novel genes, including Isthmin 1, Tetraspanin 33 (TSPAN33), and Meteorin-like (6–8). In this article, we report an uncharacterized gene ( C17orf99 ; chromosome 17 open reading frame 99) that encodes a small secreted protein (~27 kDa) produced by B cells upon activation.…”

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confidence: 99%

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Identification of IL-40, a Novel B Cell–Associated Cytokine

Catalán-Dibene

Vazquez

Luu

et al. 2017

The Journal of Immunology

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We describe a novel B cell–associated cytokine, encoded by an uncharacterized gene (C17orf99; chromosome 17 open reading frame 99), that is expressed in bone marrow and fetal liver and whose expression is also induced in peripheral B cells upon activation. C17orf99 is only present in mammalian genomes, and it encodes a small (~27-kDa) secreted protein unrelated to other cytokine families, suggesting a function in mammalian immune responses. Accordingly, C17orf99 expression is induced in the mammary gland upon the onset of lactation, and a C17orf99−/− mouse exhibits reduced levels of IgA in the serum, gut, feces, and lactating mammary gland. C17orf99−/− mice have smaller and fewer Peyer’s patches and lower numbers of IgA-secreting cells. The microbiome of C17orf99−/− mice exhibits altered composition, likely a consequence of the reduced levels of IgA in the gut. Although naive B cells can express C17orf99 upon activation, their production increases following culture with various cytokines, including IL-4 and TGF-β1, suggesting that differentiation can result in the expansion of C17orf99-producing B cells during some immune responses. Taken together, these observations indicate that C17orf99 encodes a novel B cell–associated cytokine, which we have called IL-40, that plays an important role in humoral immune responses and may also play a role in B cell development. Importantly, IL-40 is also expressed by human activated B cells and by several human B cell lymphomas. The latter observations suggest that it may play a role in the pathogenesis of certain human diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of IL-40, a Novel B Cell–Associated Cytokine

Catalán-Dibene

Vazquez

Luu

et al. 2017

The Journal of Immunology

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“…Total RNA was isolated and gene expression measured by real time PCR as described [6]. qPCR results are plotted as ratios relative to the control gene 18S in universal strand cDNA [13].…”

Section: Methodsmentioning

confidence: 99%

“…This screen led to the identification of several unknown or poorly characterized genes encoding secreted or transmembrane proteins expressed by various cells of the immune system. We have recently reported two of these molecules; the first one is a transmembrane protein that represents a novel biomarker of activated B cells (TSPAN33) [6]; the second is a secreted protein (Isthmin 1) expressed in the skin, mucosa and by NK, NKT and Th17 cells [7]. …”

Section: Introductionmentioning

confidence: 99%

METEORIN-LIKE is a cytokine associated with barrier tissues and alternatively activated macrophages

Ushach

Burkhardt

Martinez

et al. 2015

Clinical Immunology

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105

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Cytokines are involved in many functions of the immune system including initiating, amplifying and resolving immune responses. Through bioinformatics analyses of a comprehensive database of gene expression (BIGE: Body Index of Gene Expression) we observed that a small secreted protein encoded by a poorly characterized gene called meteorin-like (METRNL), is highly expressed in mucosal tissues, skin and activated macrophages. Further studies indicate that Metrnl is produced by Alternatively Activated Macrophages (AAM) and M-CSF cultured bone marrow macrophages (M2-like macrophages). In the skin, METRNL is expressed by resting fibroblasts and IFNγ-treated keratinocytes. A screen of human skin-associated diseases showed significant over-expression of METRNL in psoriasis, prurigo nodularis, actinic keratosis and atopic dermatitis. METRNL is also up-regulated in synovial membranes of human rheumatoid arthritis. Taken together, these results indicate that Metrnl represents a novel cytokine, which is likely involved in both innate and acquired immune responses.

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The Neonatal and Adult Human Testis Defined at the Single-Cell Level

et al. 2019

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SUMMARY Spermatogenesis has been intensely studied in rodents but remains poorly understood in humans. Here, we used single-cell RNA sequencing to analyze human testes. Clustering analysis of neonatal testes reveals several cell subsets, including cell populations with characteristics of primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). In adult testes, we identify four undifferentiated spermatogonia (SPG) clusters, each of which expresses specific marker genes. We identify protein markers for the most primitive SPG state, allowing us to purify this likely SSC-enriched cell subset. We map the timeline of male germ cell development from PGCs through fetal germ cells to differentiating adult SPG stages. We also define somatic cell subsets in both neonatal and adult testes and trace their developmental trajectories. Our data provide a blueprint of the developing human male germline and supporting somatic cells. The PGC-like and SSC markers are candidates to be used for SSC therapy to treat infertility.

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TSPAN33 is a novel marker of activated and malignant B cells

Cited by 24 publications

References 69 publications

Identification of IL-40, a Novel B Cell–Associated Cytokine

Identification of IL-40, a Novel B Cell–Associated Cytokine

METEORIN-LIKE is a cytokine associated with barrier tissues and alternatively activated macrophages

The Neonatal and Adult Human Testis Defined at the Single-Cell Level

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