Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells

Medina, Francisco J.; Segundo, Carmen; Campos‐Caro, Antonio; Salcedo, I; García-Poley, Antonio; Brieva, José A.

doi:10.1136/gut.52.3.383

Cited by 31 publications

(35 citation statements)

References 48 publications

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“…1D) (29,31,39). Expression of CD27 was low in both subsets, in agreement with previous findings (34,35) (data not shown).…”

Section: Importancesupporting

confidence: 91%

“…High expression of the transcription factor IRF4 is characteristic of both PB and PC (24)(25)(26), while expression of CD138 is most often associated with PC differentiation (27,28). Consistent with other reports and through backgating analysis of IRF4 hi populations of interest, these PC/PB subsets were identified as lacking expression of CD20 (29)(30)(31)(32) but as CD19 ϩ/Ϫ (31,33,34). Thus, for all sites examined, PB were identified as CD20 Ϫ IRF4 hi CD138 Ϫ and PC as CD20 Ϫ IRF4 hi CD138 ϩ (Fig.…”

Section: Importancesupporting

confidence: 85%

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Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Shaw

Miller-Novak

Mohanram

et al. 2017

J Virol

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In a recent study, we found that protection following simian immunodeficiency virus (SIV) exposure correlated with rectal plasma cell frequency in vaccinated female rhesus macaques. We sought to determine if the same macaques maintained high mucosal plasma cell frequencies postinfection and if this translated to reduced viremia. Although delayed SIV acquisition did not predict subsequent viral control, alterations existed in the distribution of plasma cells and plasmablasts between macaques that exhibited high or low viremia. Flow cytometric analysis of cells from rectal biopsy specimens, bone marrow, and mesenteric lymph nodes of vaccinated infected, unvaccinated infected, and uninfected macaques identified two main IRF4 hi subsets of interest: CD138 ϩ plasma cells, and CD138 Ϫ plasmablasts. In rectal tissue, plasma cell frequency positively correlated with plasma viremia and unvaccinated macaques had increased plasma cells and plasmablasts compared to vaccinated animals. Likewise, plasmablast frequency in the mesenteric lymph node correlated with viremia. However, in bone marrow, plasmablast frequency negatively correlated with viremia. Accordingly, low-viremic macaques had a higher frequency of both bone marrow IRF4 hi subsets than did animals with high viremia. Significant reciprocal relationships between rectal and bone marrow plasmablasts suggested that efficient trafficking to the bone marrow as opposed to the rectal mucosa was linked to viral control. mRNA expression analysis of proteins involved in establishment of plasma cell niches in sorted bone marrow and rectal cell populations further supported this model and revealed differential mRNA expression patterns in these tissues.IMPORTANCE As key antibody producers, plasma cells and plasmablasts are critical components of vaccine-induced immunity to human immunodeficiency virus type 1 (HIV-1) in humans and SIV in the macaque model; however, few have attempted to examine the role of these cells in viral suppression postinfection. Our results suggest that plasmablast trafficking to and retention in the bone marrow play a previously unappreciated role in viral control and contrast the potential contribution of mucosal plasma cells to mediate protection at sites of infection with that of bone marrow plasmablasts and plasma cells to control viremia during chronic infection. Manipulation of niche factors influencing the distribution and maintenance of these critical antibody-secreting cells may serve as potential therapeutic targets to enhance antiviral responses postvaccination and postinfection.

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“…1D) (29,31,39). Expression of CD27 was low in both subsets, in agreement with previous findings (34,35) (data not shown).…”

Section: Importancesupporting

confidence: 91%

Section: Importancesupporting

confidence: 85%

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Shaw

Miller-Novak

Mohanram

et al. 2017

J Virol

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“…4 and 7). Similar to alterations in surface phenotype, these molecular changes recapitulate the differential expression of Pax-5, Blimp-1 and XBP-1 observed for mature B cells and primary PC (3,5,7,36,38), and complement our recent report of gene expression by ISC generated from mouse B cells in vitro in response to T celldependent stimuli (43). Similar observations regarding expression of transcription factors have been obtained for human B cells activated in vitro to differentiate toward ISC (38,39), or in murine splenic B cells following immunization (45).…”

Section: Discussionmentioning

confidence: 54%

“…3 In humans, PC can be identified by the up-regulation in expression of CD38 and the concomitant decrease in CD20 (CD38 ϩϩ CD20 Ϯ ) (1,2). Cells with this phenotype have been detected in lymphoid tissues such as spleen (3), tonsils (4,5), intestine (6,7), bone marrow (BM), and peripheral blood (1,5). Importantly, PC are overrepresented not only in malignancies (2,8), but also autoimmune disorders such as systemic lupus erythematosus (9,10).…”

Section: O Ne Of the Primary Functions Of Mature B Cells Is The Produmentioning

confidence: 99%

Increased Expression of CD27 on Activated Human Memory B Cells Correlates with Their Commitment to the Plasma Cell Lineage

Avery

Ellyard

Mackay

et al. 2005

The Journal of Immunology

123

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Plasma cells (PC) or Ig-secreting cells (ISC) are terminally differentiated B cells responsible for the production of protective Ig. ISC can be generated in vitro by culturing human B cells with the T cell-derived stimuli CD40L, IL-2, and IL-10. ISC have traditionally been identified by the increased expression of CD38, analogous to primary human PC, and the acquired ability to secrete Ig. By tracking the proliferation history of activated B cells, we previously reported that the differentiation of memory B cells into CD38+ B cells is IL-10 dependent, and increases in frequency with cell division. However, <50% of CD38+ cells secreted Ig, and there was a population of CD38− ISC. Thus, the PC phenotype of CD38+ cells generated in vitro did not correlate with PC function. To address this, we have examined cultures of activated memory B cells to accurately identify the phenotype of ISC generated in vitro. We found that CD27 is also up-regulated on memory B cells in an IL-10-dependent and division-dependent manner, and that ISC segregated into the CD27high subset of activated memory B cells irrespective of the acquired expression of CD38. The ISC generated in these cultures expressed elevated levels of the transcription factors Blimp-1 and X box-binding protein-1 and reduced levels of Pax-5, and exhibited selective migration toward CXCL12, similar to primary PC. We propose that the differentiation of memory B cells into PC involves a transitional stage characterized by a CD27highCD38− phenotype with the acquired ability to secrete high levels of Ig.

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“…Previous studies have established that, in humans, there is a gradient of increasing maturity from early PC (tonsil), to transitional/circulating PC (blood) to PC obtained from deposit organs (BM and mucose lamina propria) (20,43). Although all of these PC populations expressed detectable amounts of mRNA for PDRI-BF1/Blimp-1 (20,44), the relative quantities of this important factor present in each of them have not been analyzed yet. Accordingly, mRNA for this transcription factor was determined in PC isolated from the different territories by quantitative real-time RT-PCR.…”

Section: Comparison Between Blood Tetcmentioning

confidence: 99%

Immunization-Induced Perturbation of Human Blood Plasma Cell Pool: Progressive Maturation, IL-6 Responsiveness, and High PRDI-BF1/BLIMP1 Expression Are Critical Distinctions between Antigen-Specific and Nonspecific Plasma Cells

González-Garcı́a

Ocaña

Jiménez-Gómez

et al. 2006

The Journal of Immunology

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The present study shows that reimmunization with tetanus toxoid (tet) caused a transient increase of the human blood plasma cell (PC) pool, detectable from 6th to 15th day postboost, as well as the temporal alteration of several PC features. Labeling of specific PC with FITC-tet C fragment (tetC) allowed kinetics analysis of the tetC+ and tetC− PC, and revealed remarkable differences between them: 1) the kinetics of tetC+ PC occurrence was exponential, and most of them appeared in a narrow time frame (5th to 8th day postboost), whereas the tetC− PC increase was lower (three to five times) and more prolonged (4th to 15th day postboost). 2) The tetC+ PC subset contained a fraction of cycling cells, expressed high levels of DR, CD138, and CD126, and responded to IL-6 by improving their survival and Ig secretion; in contrast, the tetC− PC showed higher CXCR4 and lower DR and CD138, did not respond to IL-6, and contained a fraction of apoptotic cells. 3) Sequential phenotypic analysis revealed maturational changes within the tetC+, but not tetC−, PC subset; sequencing of tetC+ PC IgVH genes showed clear features of Ag selection. 4) The tetC+ PC expressed several times more positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1 transcription factor than the tetC− PC. 5) The tetC− PC and bone marrow resident PC similarly expressed low DR and high CXCR4, but differed in that the latter exhibited higher levels of CD31, CD138, and positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1. These findings support the view that tetC+ PC contain bone marrow PC precursors, and tetC− PC probably belong to a removable compartment of aged PC.

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Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells

Cited by 31 publications

References 48 publications

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Increased Expression of CD27 on Activated Human Memory B Cells Correlates with Their Commitment to the Plasma Cell Lineage

Immunization-Induced Perturbation of Human Blood Plasma Cell Pool: Progressive Maturation, IL-6 Responsiveness, and High PRDI-BF1/BLIMP1 Expression Are Critical Distinctions between Antigen-Specific and Nonspecific Plasma Cells

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Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells

Cited by 31 publications

References 48 publications

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Increased Expression of CD27 on Activated Human Memory B Cells Correlates with Their Commitment to the Plasma Cell Lineage

Immunization-Induced Perturbation of Human Blood Plasma Cell Pool: Progressive Maturation, IL-6 Responsiveness, and High PRDI-BF1/BLIMP1 Expression Are Critical Distinctions between Antigen-Specific and Nonspecific Plasma Cells

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Resources

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Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia

Influence of Plasma Cell Niche Factors on the Recruitment and Maintenance of IRF4 ^hi Plasma Cells and Plasmablasts in Vaccinated, Simian Immunodeficiency Virus-Infected Rhesus Macaques with Low and High Viremia