Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

Willard-Mack, Cynthia L.; Elmore, Susan A.; Hall, William C.; Harleman, Johannes H.; Kuper, C. Frieke; Losco, Patricia E.; Rehg, Jerold E.; Rühl-Fehlert, Christine; Ward, Jerrold M.; Weinstock, Daniel; Bradley, Alys; Hosokawa, Satoru; Pearse, Gail; Mahler, Beth; Herbert, Ronald A.; Keenan, Charlotte M.

doi:10.1177/0192623319867053

Cited by 66 publications

(95 citation statements)

References 184 publications

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“…The term 'infiltrate' is preferred over the term 'inflammation' (i.e. lymphadenitis) due to the lack of degenerative or vascular changes in the examined LNs (51,52). Neutrophil infiltrate was more evident in the tissues sampled 3h than in those sampled 24h post injection, in agreement with the known rapid recruitment of these cells to sites of infection or tissue injury and the short half-lives of neutrophils (53).…”

Section: Discussionmentioning

confidence: 56%

The impact of size on particle drainage dynamics and antibody response

Zinkhan

Ogrina

Baļķe

et al. 2020

Preprint

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Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B-cells and other innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T=3 icosahedron particles. They can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxoid (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T=3, with a diameter of ∼30nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, ∼1µm in length and ∼30nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTT-VLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Round-shaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge antigen-presenting cells as well as B-cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced immune response towards TH1. Up to our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedrons or rods in the micrometer size.

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Section: Discussionmentioning

confidence: 56%

The impact of size on particle drainage dynamics and antibody response

Zinkhan

Ogrina

Baļķe

et al. 2020

Preprint

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“…About 50% of the lymphocytic population expresses T cell marker CD3, and 50% expresses B cell marker CD20. The heterogeneity of the lymphocytic population and the absence of lymphoma in other tissues did not support the hypothesis of an IDC hyperplasia-associated lymphoma 13 . The proliferation of follicular dendritic cells (FDC) from germinal centers can also be ruled out, as FDCs are negative for F4/80 and do not originate from the monocyte/macrophage lineage.…”

mentioning

confidence: 60%

“…IDC is the specific designation of dendritic cells located in the T-cell area of secondary lymphoid tissues (lymph nodes and spleen). This benign lesion is interpreted in the literature as a response to the presence of antigen in tissues drained by the lymph nodes 13 . Hyperplasia of IDC in paracortical T cell areas is generally seen in response to viral infection or irradiation.…”

mentioning

confidence: 99%

“…In mice, the differential diagnosis for interdigitating DC hyperplasia also includes histiocytic proliferative disorders, such as macrophage hyperplasia, sinus histiocytosis, histiocytic sarcoma (HS), and histiocyte-associated lymphoma (HAL) 13 . Sinus histiocytosis is characterized by the conservation of a normal lymph node architecture, with an accumulation of macrophages in the subcapsular and medullary sinuses, which was not observed in the present case 8 .…”

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confidence: 99%

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Characterization of an interdigitating dendritic cell hyperplasia case in a lymph node of a control C57BL/6 mouse

et al. 2021

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Interdigitating dendritic cell (IDC) hyperplasia is considered a benign spontaneous condition occasionally observed in the lymph nodes of mice. It has been rarely reported and, to the best of our knowledge, it has never been characterized using immunohistochemistry. The present work describes a spontaneous IDC hyperplasia case in a lymph node of a 16-week-old control female C57BL/6 mouse. Microscopically, the lymph node architecture was completely effaced by the proliferation of eosinophilic spindle cells with an abundant pale cytoplasm forming trabecule admixed lymphocyte infiltrates. The spindle cell population was positive for F4/80, partially positive for S100 calcium-binding protein A4 (S100A4), slightly positive for E-cadherin, and negative for α-Smooth muscle actin (SMA) and cytokeratin. Lymphocytes were positive for CD3, CD4, CD20 and negative for CD8. Spindle cells were considered to be originated from the myeloid lineage, based on the immunohistochemistry (IHC) results, but their precise origin remains unclear (IDC or macrophages); even if macrophage origin is most likely based on F4/80 positivity, this remains to be further clarified using other markers.

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“…1 In the thymic proliferative lesions, the proliferative cells originated from the thymic epithelial cells in both cortex-like LyR and MD areas; however, it was difficult to recognize the proliferative thymic epithelial cells in the cortex-like LyR area due to the prominently increased number of lymphocytes observed in hematoxylin and eosin–stained specimens. 2 There are various types of thymic epithelia in the normal thymus, such as cortical, medullary, and subcapsular types. 3 In humans, the cortical thymic epithelium is positive for cytokeratin (CK) 8, CK18, and CK19; medullary thymic epithelium is positive for CK5, CK7, CK8, CK14, CK18, and CK19 4,5 ; and subcapsular epithelium is positive for CK14.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Characteristics of Thymomas and Hyperplastic Lesions in Wistar Hannover Rats

Tomonari¹,

Sato²,

Yamada³

et al. 2020

Toxicol Pathol

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Previously, we investigated the higher incidence of hyperplastic lesions and thymomas and histopathological resemblance of cortex–medullary structures between thymomas and normal thymuses in Wistar Hannover (WH) rats. Thymomas had pale-staining cell foci (PA) similar to medulla but without lymphocytes. Here, we focused on the differences in cytokeratin (CK) expression in the thymic epithelia of the cortex and medulla and compared the structures of thymomas and normal thymuses. Thymomas, hyperplastic lesions, and normal thymuses obtained from background studies of WH rats were stained with antibodies against CK14, CK18, and CD20. In normal thymuses, the epithelial cells were positive for CK14 in the medulla and subcapsular area and for CK18 in the cortex, B-cells were positive for CD20 in the medulla. In thymomas, the epithelial cells were positive for CK14 in the medullary differentiation (MD) areas and for CK18 in the cortex-like lymphocyte rich and PA, and B-cells were positive for CD20 in the MD areas.

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Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

Cited by 66 publications

References 184 publications

The impact of size on particle drainage dynamics and antibody response

The impact of size on particle drainage dynamics and antibody response

Characterization of an interdigitating dendritic cell hyperplasia case in a lymph node of a control C57BL/6 mouse

Immunohistochemical Characteristics of Thymomas and Hyperplastic Lesions in Wistar Hannover Rats

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