Reticulum Arrangement Related to the Behavior of Cell Populations in the Mouse Lymph Node

Author(s):  
Maria A. B. de Sousa
Keyword(s):  
2012 ◽  
Vol 52 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Idania Marrero ◽  
Allen Vong ◽  
Yang Dai ◽  
Joanna D. Davies

1978 ◽  
Vol 41 (2) ◽  
pp. 276-285 ◽  
Author(s):  
George L. Manderino ◽  
Abram B. Stavitsky

1974 ◽  
Vol 139 (4) ◽  
pp. 1002-1012 ◽  
Author(s):  
John A. van Boxel ◽  
David L. Rosenstreich

Heat-aggregated guinea pig γ-globulin was shown to bind to the surface membrane of a subclass of guinea pig T lymphocytes. Cells of this subpopulation were identified as T lymphocytes because these cells did not stain for surface Ig (a B-cell marker) but did form spontaneous E-rosettes with rabbit erythrocytes (a T-cell marker). A strikingly high proportion of such aggregate-binding (Agg+), E-rosette-forming (E-rosette+), but surface Ig-negative (Ig-) cells were found in an inflammatory exudate. Thus purified peritoneal exudate lymphocytes (PELs) are known to consist of over 90% T cells, and 59% of these cells bound aggregates. 10% of these Agg+ Ig- E-rosette+ cells were found in draining lymph node cell populations and none in thymus cell populations. The high frequency amongst PELs suggested that these Aggregate+ Ig- E-rosette+ cells might be activated T cells as these are known to occur in high proportion in PEL populations. Confirmatory evidence for this postulate was provided by the striking increase (from 10% to 46%) of Ig- E-rosette+ cells that bound aggregates when lymph node cells were activated by antigen stimulation in vitro.


1978 ◽  
Vol 45 (1) ◽  
pp. 116-127 ◽  
Author(s):  
Charles E. Tanner ◽  
Hai-Choo Lim ◽  
Gaetan Faubert

1978 ◽  
Vol 41 (2) ◽  
pp. 264-275 ◽  
Author(s):  
George L. Manderino ◽  
Gary T. Gooch ◽  
Abram B. Stavitsky

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3725-3725
Author(s):  
Anna Wing ◽  
Wenzhao Meng ◽  
Gerald Wertheim ◽  
Dale Frank ◽  
Michele Paessler ◽  
...  

Abstract Introduction: Castleman disease (CD) is an uncommon lymphoproliferative disorder of unclear etiology. CD is broadly subclassified into unicentric (UCD) and multicentric (MCD) disease based on based on clinical, radiological, laboratory and histomorphological findings. UCD presents with minimal symptoms, is restricted to a single lymph node station, and excision is usually curative. Multicentric CD, in contrast, presents with systemic inflammatory symptoms, multicentric lymphadenopathy, and vital organ dysfunction. MCD is further subclassified into Human Herpesvirus-8(HHV-8)-associated MCD and HHV-8-negative/idiopathic MCD (iMCD), the etiology of which is poorly understood. Histologically, UCD frequently shows a hyaline vascular pattern with atretic follicles, thickened mantle zones and increased interfollicular vascularity with hyalinization. iMCD frequently shows increased interfollicular plasma cells and hyperplastic follicles. iMCD is also characterized by a systemic hypercytokinemia that includes IL-6, VEGF, IL-2, TNF-α, IL-10 and CXCL13. However, the cell(s) involved in initiating and amplifying the cytokine network are unclear. We combined histomorphology and cytokine in situ hybridization to identify the hypercytokine-producing cells in lymph nodes from CD patients. In addition, T and B lymphocytes play important roles in initiating and amplifying the cytokine response and their clonality has not been well-studied in CD. Here, we performed deep sequencing of the immunoglobulin heavy chain and T cell receptor gene loci. Methods: Lymph node biopsies from patients with UCD and iMCD were identified from the pathology archives of the Children's Hospital of Philadelphia. 17 UCD cases and 8 HHV8-negative iMCD cases were examined. Reactive lymph nodes (N=10) with plasmacytosis and/or other CD-like features served as controls. Cytokine expression was determined by RNA in situ hybridization (RNAscope) on formalin fixed paraffin embedded tissue. IL-6, IL-6R, VEGF, IL-10, TNF-α, IL-1β, IL-2, and IL-8 RNA expression patterns were analyzed in conjunction with histomorphological features. Expression was manually quantified with a semi-quantitative grading scale (0-4) per manufacturer recommendations and statistical analysis was performed using the Chi-square test. Fresh frozen lymph node tissue was utilized for deep sequencing of the TCR Vβ and IgH gene loci. VDJ usage, clonal frequency and CDR3 sequence was determined and compared between subtypes of CD and reactive lymph node controls. Results: Lymph nodes from patients with iMCD express significantly higher levels of VEGF compared to patients with UCD and controls (75% vs. 29% vs. 0%; p=0.014). Atretic follicles and interfollicular regions were the source of increased VEGF expression. Potential cell types responsible for the increased VEGF production in these regions are follicular dendritic cells in the atretic follicles and plasma cells in the interfollicular areas. IL-6 expression was also significantly higher in iMCD cases compared to UCD and controls (75% vs. 25% vs. 20%, p=0.026) in a subset of cells within the interfollicular regions. This cellular source of the excess IL-6 in the interfollicular region may be endothelial cells. Thus, follicular dendritic cells in the germinal centers and endothelial cells, T cells, and plasma cells in the interfollicular spaces are potential sources for increased VEGF and IL-6. IL-6R, IL-10, TNF-α, IL-1β, IL-2, and IL-8 showed no significant differences between the various subtypes of CD. Deep sequencing of the TCRα gene loci revealed mildly expanded clonal T-cell populations (5% of total sequences) in a subset of iMCD cases (2/6) and UCD cases (1/9) compared to controls (0/15). B cell populations were polyclonal in both subtypes of CD and in reactive lymph nodes. Conclusion: The findings suggest that cells in the interfollicular region and atretic follicles in the lymph nodes are a potential source of the systemic hypercytokinemia in iMCD. The locations and patterns of cytokine expression implicate follicular dendritic cells, endothelial cells, and plasma cells specifically as potential hypercytokine-producing cells. Additionally, T cells in CD show oligoclonality in some cases and may play an important role in initiating or amplifying the immune response in CD. Disclosures Fajgenbaum: Janssen Pharmaceuticals, Inc.: Research Funding.


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