B‐cell activation with CD40L or CpG measures the function of B‐cell subsets and identifies specific defects in immunodeficient patients

Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Mortari, Eva Piano; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

doi:10.1002/eji.201646574

Cited by 55 publications

(80 citation statements)

References 22 publications

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“…We set out to use a stimulation protocol that maximises B‐cell differentiation into antibody‐secreting cells (ASCs), otherwise called plasmablasts, in order to mimic a robust in vivo response. It is increasingly apparent that robust B‐cell differentiation requires innate Toll‐like‐receptor (TLR) signals, adaptive BCR signals and T cell helper signals such as IL‐21 and CD40L . Similarly, it has been established that B‐cell subsets will not differentiate in the absence of non‐B cells .…”

Section: Introductionmentioning

confidence: 99%

“…It is increasingly apparent that robust Bcell differentiation requires innate Toll-likereceptor (TLR) signals, adaptive BCR signals and T cell helper signals such as IL-21 and CD40L. [3][4][5][6][7][8][9] Similarly, it has been established that B-cell subsets will not differentiate in the absence of non-B cells. 9,10 Agonists of TLR7/8 (R848) and TLR9 (CpG) induce similar gene expression in human Bcells.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9] Similarly, it has been established that B-cell subsets will not differentiate in the absence of non-B cells. 9,10 Agonists of TLR7/8 (R848) and TLR9 (CpG) induce similar gene expression in human Bcells. 11 R848 and, to a lesser extent, CpG are also sufficient to induce differentiation of memory Bcells, but not of naive B-cells.…”

Section: Introductionmentioning

confidence: 99%

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Distinguishing naive‐ from memory‐derived human B cells during acute responses

et al. 2019

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Objectives A fundamental question in influenza research is whether antibody titre decline upon successive exposure to variant strains is consequent to recall of cross‐reactive memory B cells that competitively inhibit naive B‐cell responses. In connection, it is not clear whether naive and memory B cells remain phenotypically distinct acutely after activation such that they may be distinguished ex vivo. Methods Here, we first compared the capacity of anti‐Ig and Toll‐like‐receptor (TLR) 7/8 and TLR9 agonists (R848 and CpG) to augment human B‐cell differentiation induced by IL‐21 and sCD40L. The conditions that induced optimal differentiation were then used to compare the post‐activation phenotype of sort‐purified naive and memory B‐cell subsets by FACS and antibody‐secreting cell (ASC) ELISPOT. Results Sort‐purified naive and memory B cells underwent robust plasmablast and ASC formation when stimulated with R848, but not CpG, and co‐cultured with monocytes. This coincided with increased IL‐1β and IL‐6 production when B cells were co‐cultured with monocytes and stimulated with R848, but not CpG. Naive B cells underwent equivalent ASC generation, but exhibited less class‐switch and modulation of CD27, CD38 and CD20 expression than memory B cells after stimulation with R848 and monocytes for 6 days. Conclusion Stimulation with R848, IL‐21 and sCD40L in the presence of monocytes induces robust differentiation and ASC generation from both naive and memory B‐cells. However, naive and memory B cells retain key phenotypic differences after activation that may facilitate ex vivo discrimination and better characterisation of acute responses to variant antigens.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distinguishing naive‐ from memory‐derived human B cells during acute responses

et al. 2019

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“…On the contrary, there are several evidences that have shown the correct IgA production when a deficiency exists in CD40 or CD40L in humans and mice, for instance, in experimental murine with rotavirus infection, virus clearance was achieved via induction of specific IgA, even in T-cell deficient animals [59, 84, 85]. Although some studies have proposed a possible CD40L deficiency in SIgAD patients, B cells of patients showed a reduced proliferative response to CD40L [86], and further support the idea that the probability of T-cell deficiency in SIgAD patients is low.…”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

Bagheri¹,

Sanaei²,

Yazdani³

et al. 2019

Int Arch Allergy Immunol

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Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.

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“…We hope that our new Letters section will match the interest of the content that we currently publish and that Letters will feature in the top accessed articles next year, joining top accessed articles such as those from 2017 that cover immunodeficiency, cancer and innate immunity to name just a few.…”

mentioning

confidence: 99%