Long-Lived Plasma Cells from Human Small Intestine Biopsies Secrete Immunoglobulins for Many Weeks In Vitro

Mesin, Luka; Niro, Roberto Di; Thompson, Keith M.; Lundin, Knut E.A.; Sollid, Ludvig M.

doi:10.4049/jimmunol.1003181

Cited by 79 publications

(82 citation statements)

References 45 publications

(59 reference statements)

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“…Among others, these include BAFF, APRIL, IGF-1, VEGF, and SDF-1a, whose signaling mechanisms are not primarily mediated through JAK-STAT pathways (19,24,31,46). Experiments in mice PCs and human mucosal PCs support the view that some of these latter factors cooperate with STAT-3-activating cytokines (namely, IL-6) to induce prolonged PC survival (19,24,31,46,47). Present data reveal that in human PCs, the expression of the receptors for these cytokines is highly heterogeneous.…”

Section: Discussionmentioning

confidence: 55%

STAT-3 Activation by Differential Cytokines Is Critical for Human In Vivo–Generated Plasma Cell Survival and Ig Secretion

Rodríguez‐Bayona

Ramos-Amaya

López-Blanco

et al. 2013

The Journal of Immunology

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Maturation and survival of plasma cells (PCs) depends on extrinsic factors provided in specialized niches. In addition, B lymphocyte differentiation into PCs requires the activation of the JAK–STAT-3 pathway. However, whether STAT-3 is needed only during the transition of B lymphocytes to PC, or it is also involved in the survival and function of PCs at different stages of maturation, has not been unequivocally clarified. This study analyzes the effect of IL-10, IL-21, and IL-6 on human in vivo–generated PCs isolated from secondary lymphoid organs, blood (circulating, recently Ag-induced PCs), and bone marrow. PCs from these different organs show specific profiles of receptors for, and responsiveness to, these cytokines required for their survival and sustained Ab secretion. However, IL-10, IL-21, and IL-6 commonly induce STAT-3 phosphorylation in the three PC subsets, and all of their effects are exerted strictly through the STAT-3 activation. The inhibition or nonactivation of this pathway in the three PC populations impairs not only the effect of STAT-3–activating cytokines, but also the action of other cytokines important at the PC level, including a proliferation-induced ligand, BAFF, insulin-like growth factor 1, vascular endothelial growth factor, and stromal cell–derived factor-1α. These results indicate that STAT-3 activation is critical for human PCs throughout their maturation.

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Section: Discussionmentioning

confidence: 55%

STAT-3 Activation by Differential Cytokines Is Critical for Human In Vivo–Generated Plasma Cell Survival and Ig Secretion

Rodríguez‐Bayona

Ramos-Amaya

López-Blanco

et al. 2013

The Journal of Immunology

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“…If the gut PCs have a short life span, it is unlikely that replenishment of TG2-specific PCs by rare memory B cells alone can explain the maintenance of this cell population, particularly in the absence of stimulating Ag. Several reports argue that intestinal PCs that are generated in germinal centers are indeed long-lived, both in humans and in mice (15,18,44), and it could therefore be that some TG2-specific PCs are long-lived, possibly throughout the lifetime of patients. were generated to all clusters of clones that include sequences from five cells or more with at least one PC sequence (n = 2368).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Celiac Disease Autoreactive Gut Plasma Cells and Their Corresponding Memory Compartment in Peripheral Blood Using High-Throughput Sequencing

Snir

Mesin

Gidoni

et al. 2015

The Journal of Immunology

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Autoreactive IgA plasma cells (PCs) specific for the enzyme transglutaminase 2 (TG2) are abundant in the small intestine of patients with active celiac disease (CD), and their number drops in patients treated by dietary gluten elimination. Little is known about their characteristics and their role in the disease. In this study, using high-throughput sequencing of the IgH V region (IGHV) genes, we have studied features of TG2-specific PCs and their related B cell clones in peripheral blood. We found that TG2-specific PCs from both untreated and treated patients have acquired lower number of somatic hypermutation and used focused IGHV repertoire with overrepresentation of the IGHV3-48, IGHV4-59, IGHV5-10-1, and IGHV5-51 gene segments. Furthermore, these PCs were clonally expanded and showed signs of affinity maturation. Lineage trees demonstrated shared clones between gut PCs and blood memory B cells, primarily IgAs. Some trees also involved IgG cells, suggesting that anti-TG2 IgA and IgG responses are related. Similarly to TG2-specific PCs, clonally related memory IgA B cells of blood showed lower mutation rates with biased usage of IGHV3-48 and IGHV5-51. Such memory cells were rare in peripheral blood, yet detectable in most patients assessed by production of anti-TG2 Abs in vitro following stimulation of cells from patients who had been on a long-term gluten-free diet. Thus, the Ab response to TG2 in CD, while maintaining its IGHV gene usage, is dynamically regulated in response to gluten exposure with a low degree of maintenance at both PC and memory B cell levels in patients in remission.

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“…The relative significance of differences between fish vaccinated with either the empty plasmid or empty microspheres and vaccinated fish at each segment of the digestive tract was determined through a one-way ANOVA and is shown above the bars as *. doi:10.1371/journal.pone.0066118.g005 oligo (dT) [12][13][14][15][16][17][18] (0.5 mg/ml) following the manufacturer's instructions. The resulting cDNA was diluted and stored at 220uC.…”

Section: Cdna Preparationmentioning

confidence: 99%

“…However, even if IgT plays an important role in mucosal immunity, some teleost species, such as channel catfish, do not seem to have an IgT or IgZ-like sequence but do present a specific mucosal response [12,13]. Therefore, it seems probable that local IgM mucosal responses play an important role together with IgT responses, as in mammals both IgA and IgMspecific plasma cells have been proved to play a combined role in mucosal immunity [14,15].…”

Section: Introductionmentioning

confidence: 99%

The pyloric caeca area is a major site for IgM+ and IgT+ B cell recruitment in response to oral vaccination in rainbow trout

Ballesteros¹,

Saint-Jean²,

Pérez-Prieto³

et al. 2013

Fish & Shellfish Immunology

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Although previous studies have characterized some aspects of the immune response of the teleost gut in response to diverse pathogens or stimuli, most studies have focused on the posterior segments exclusively. However, there are still many details of how teleost intestinal immunity is regulated that remain unsolved, including the location of IgM + and IgT + B cells along the digestive tract and their role during the course of a local stimulus. Thus, in the current work, we have studied the B cell response in five different segments of the rainbow trout (Oncorhynchus mykiss) digestive tract in both naïve fish and fish orally vaccinated with an alginate-encapsulated DNA vaccine against infectious pancreatic necrosis virus (IPNV). IgM + and IgT + cells were identified all along the tract with the exception of the stomach in naïve fish. While IgM + cells were mostly located in the lamina propria (LP), IgT + cells were primarily localized as intraepithelial lymphocytes (IELs). Scattered IgM + IELs were only detected in the pyloric caeca. In response to oral vaccination, the pyloric caeca region was the area of the digestive tract in which a major recruitment of B cells was demonstrated through both real time PCR and immunohistochemistry, observing a significant increase in the number of both IgM + and IgT + IELs. Our findings demonstrate that both IgM + and IgT + respond to oral stimulation and challenge the paradigm that teleost IELs are exclusively T cells. Unexpectedly, we have also detected B cells in the fat tissue associated to the digestive tract that respond to vaccination, suggesting that these cells surrounded by adipocytes also play a role in mucosal defense.

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Long-Lived Plasma Cells from Human Small Intestine Biopsies Secrete Immunoglobulins for Many Weeks In Vitro

Cited by 79 publications

References 45 publications

STAT-3 Activation by Differential Cytokines Is Critical for Human In Vivo–Generated Plasma Cell Survival and Ig Secretion

STAT-3 Activation by Differential Cytokines Is Critical for Human In Vivo–Generated Plasma Cell Survival and Ig Secretion

Analysis of Celiac Disease Autoreactive Gut Plasma Cells and Their Corresponding Memory Compartment in Peripheral Blood Using High-Throughput Sequencing

The pyloric caeca area is a major site for IgM+ and IgT+ B cell recruitment in response to oral vaccination in rainbow trout

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