scholarly journals Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers.

1996 ◽  
Vol 184 (5) ◽  
pp. 1927-1937 ◽  
Author(s):  
L Martínez-Pomares ◽  
M Kosco-Vilbois ◽  
E Darley ◽  
P Tree ◽  
S Herren ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
B Cell ◽  
Marginal Zone ◽  
Chimeric Protein ◽  
Mannose Receptor ◽  
Germinal Centers ◽  
White Pulp ◽  
Subcapsular Sinus ◽  
Splenic White Pulp

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.

scholarly journals The Three-dimensional Structure of Human Splenic White Pulp Compartments

2003 ◽  
Vol 51 (5) ◽  
pp. 655-663 ◽  
Author(s):  
Birte Steiniger ◽  
Lars Rüttinger ◽  
Peter J. Barth
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
Marginal Zone ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
White Pulp ◽  
Cell Region ◽  
Human Spleen ◽  
Splenic White Pulp

The precise arrangement of B- and T-lymphocytes in the different compartments of the human splenic white pulp is still largely unknown. We therefore performed a 3D reconstruction of 150 serial sections of a representative adult human spleen alternately stained for CD3 and CD20. The results indicate that the T-cell regions of human spleens may be interrupted by B-cell follicles. Therefore, there is no continuous periarteriolar lymphatic T-cell sheath (PALS) around white pulp arterioles. An arteriole may be surrounded by T-lymphocytes at one level, then run across a follicle without any T-cells around, and finally re-enter a T-cell region. T- and B-cell compartments are intricately interdigitated in the human splenic white pulp. CD4+ T-lymphocytes and the typical fibroblasts of the T-cell region may extend as a thin shell at the follicular surface within the marginal zone. On the other hand, IgD++ B-cells continue from the follicular outer marginal zone along the surface of the T-cell region. Our findings indicate that the microanatomy of the splenic white pulp differs between humans and rodents. This may have consequences for the immigration of recirculating lymphocytes and for initial interactions among antigen-specific T- and B-lymphocytes.

scholarly journals DISTRIBUTION OF ACID PHOSPHATASE, β-GLUCURONIDASE AND N-ACETYL-β-GLUCOSAMINIDASE ACTIVITIES IN LYMPHOCYTES OF LYMPHATIC TISSUES OF MAN AND RODENTS

1969 ◽  
Vol 17 (4) ◽  
pp. 238-243 ◽  
Author(s):  
NORIKAZU TAMAOKI ◽  
EDWARD ESSNER
Keyword(s):  
Lymph Node ◽  
Acid Phosphatase ◽  
Acid Phosphatase Activity ◽  
Germinal Centers ◽  
White Pulp ◽  
Lymphatic Tissue ◽  
Glucuronidase Activity ◽  
Splenic White Pulp ◽  
Cryostat Sections ◽  
Formalin Fixed

Acid phosphatase, β-glucuronidase and N-acetyl-β-glucosaminidase activities were demonstrated in lymphocytes of man and various rodents using formalin-fixed cryostat sections. Lymphocytes were heterogeneous in respect to the activity of these enzymes, depending on the location of cells in the lymphatic tissues. Acid phosphatase activity was demonstrable in lymphocytes located in the diffuse lymphatic tissue of the cortex of the lymph node and around the central arteriole of the splenic white pulp of all species studied. In man and in rat, the majority of lymphocytes in these areas also showed β-glucuronidase activity whereas, in the mouse, none had β-glucuronidase but many had N-acetyl-β-glucosaminidase activity. Most of the lymphocytes in the mantle of the germinal centers and in the lymphatic nodules of the splenic white pulp were negative for all three enzymes studied. The thymic lymphocytes were positive for acid phosphatase, but usually negative for β-glucuronidase and N-acetyl-β-glucosaminidase. The possible significance of these differences is discussed.

scholarly journals ROLE OF THE THYMUS IN IMMUNE REACTIONS IN RATS

1962 ◽  
Vol 116 (2) ◽  
pp. 187-206 ◽  
Author(s):  
Byron H. Waksman ◽  
Barry G. Arnason ◽  
Branislav D. Janković
Keyword(s):  
Lymph Nodes ◽  
Plasma Cells ◽  
Germinal Centers ◽  
White Pulp ◽  
Size Number ◽  
Splenic White Pulp ◽  
Spleen And Lymph Nodes ◽  
Lymphoid Nodules ◽  
Lymphatic Organs

In rats thymectomized at birth, there was a profound depletion of small lymphocytes in various lymphatic organs. In the spleen, these cells were completely lacking from the Malpighian bodies and splenic white pulp. Empty reticular structures remained surrounding the white pulp arterioles. In the lymph nodes, large masses and nodules of small lymphocytes (primary lymphoid nodules) were either markedly depleted or absent, as were the zones of these cells normally surrounding germinal centers. In both spleen and nodes, germinal centers appeared normal in size, number, and cellular make-up; and plasma cells were found in normal or even increased number in their customary position. Rats which in spite of thymectomy developed intense Arthus or delayed reactivity showed incomplete depletion of the lymphoid tissue. It is concluded that small lymphocytes of the spleen and lymph nodes may come, in large part, directly from the thymus and are not derived from medium and large lymphocytes of the germinal centers. It is suggested that there may be a second population of small lymphocytes whose function is unrelated to the thymus lymphocytes.

scholarly journals Morphometric and Histopathologic Analysis of Lymphoid Depletion in Murine Spleens Following Infection with Brucella abortus strains 2308 or RB51 or an htrA Deletion Mutant

1996 ◽  
Vol 33 (3) ◽  
pp. 282-289 ◽  
Author(s):  
M. V. Palmer ◽  
N. F. Cheville ◽  
F. M. Tatum
Keyword(s):  
Morphometric Analysis ◽  
Brucella Abortus ◽  
Marginal Zone ◽  
White Pulp ◽  
Splenic White Pulp ◽  
Lymphoid Depletion ◽  
Histopathologic Changes ◽  
Histopathologic Analysis ◽  
Marginal Zones

BALB/C mice were inoculated intraperitoneally with suspensions of Brucella abortus strains 2308 or RB51 or an htrA mutant. Spleens were examined on postinoculation day (PID) 2, 4, 7, 10, 15, 21, 30, and 60. Brucellae were cultured in high numbers from the spleens of mice infected with strains 2308 or htrA through PID 60; however, mice infected with strain RB51 cleared the infection between PID 30 and PID 60. Histopathologic changes in spleens from 2308-infected mice were characterized by marked accumulations of macrophages, which expanded marginal zones beginning as early as PID 7 and persisting through PID 60. Morphometric analysis showed a decrease in splenic white pulp in 2308-infected mice at PID 10, which correlated with the peak of bacterial infection. Although this decrease was significant ( P < 0.05) when compared with values at the previous (PID 7) and the following (PID 15) time periods, it was not significantly different from white pulp values noted at PID 2 or PID 4 or the values for control spleens. Spleens from RB51-infected mice showed only mild to moderate accumulations of macrophages in marginal zone areas during the peak of RB51 infection (PID 7-10). Morphometric analysis of RB51-infected spleens showed a decrease in white pulp area, which coincided with peak bacterial numbers. However, this decrease was not significant ( P > 0.05). Spleens from mice infected with the htrA mutant showed moderate to marked accumulations of macrophages in marginal zone areas, which persisted through PID 60. Multifocal necrosis in lymphoid follicles as early as PID 4 was seen in both htrA and 2308 infection. Morphometric analysis of htrA-infected spleens revealed no significant decrease in white pulp and no obvious correlation with bacterial numbers in the spleen. These results suggest that virulent B. abortus does not induce lymphoid depletion significantly below those values seen in noninfected mice; thus, the possible role of lymphoid depletion in the pathogenesis of brucellosis remains questionable.

scholarly journals Modeling Marginal Zone Lymphomagenesis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-31
Author(s):  
Victor Yazbeck ◽  
Ian McConnell ◽  
Emily Harris ◽  
Joseph Lownik ◽  
Ariel Sindel ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Marginal Zone ◽  
Pi3k Pathway ◽  
Marginal Zone Lymphoma ◽  
Mtor Pathway ◽  
Genetically Engineered Mouse Model ◽  
Hodgkin's Lymphomas

Introduction: Indolent B-Cell Non-Hodgkin's Lymphomas (NHL) represent a heterogeneous group of lymphoproliferative malignancies, that remain largely incurable. Marginal zone lymphomas (MZL) are the second most common subtype of indolent NHL, and lack a unique cytogenetic identifying abnormality. The B-cell receptor signaling pathway is activated in B-cell malignancy and mediates its activity mainly through the Phosphoinositide 3-kinase (PI3K) pathway. Furthermore, novel PI3K inhibitors, such as copanlisib and parsaclisib, have shown impressive clinical activity in several indolent lymphomas including MZL. This further supports the important role of the PI3K pathway in the pathogenesis of this tumor. Therefore, we hypothesized that the PI3K-mTOR pathway is sufficient for driving the pathogenesis of MZL. Methods: In order to test our hypothesis, we generated a genetically engineered mouse model carrying heterozygous global knockout alleles of both the tumor suppressor genes Phosphatase and Tensin Homolog (PTEN) and Liver Kinase B1 (LKB1). This led to over-activation of the PI3K-mTOR pathway in all mouse tissues. We closely monitored these mice for tumor formation via weekly physical examinations for several months. Upon tumor detection, the mouse was sacrificed, and tumors were sectioned for histological characterization. In order to generate a more specific model of B cells, and more accurately mimic the underlying human disease, we used the Cre-LoxP system to create the CD19-Cre-PTENfl/fl-LKB1fl/fl. Results: Thirty mice of global KO PTEN+/- LKB1 +/- died or were sacrificed due to disease progression, defined as either lymph node enlargement and/or splenomegaly. All mice showed either abnormal lymphadenopathy or splenomegaly. By Kaplan-Meier analysis, we saw a steady decrease in both tumor-free and overall survival after 3 months of age. Utilizing the product limit method, the median survival time was 6 months (95% CI: 6, 8). A total of 51 lymph nodes were sent for immunohistochemistry and pathological characterization. Of the 51 nodes, 61.5% (N=32) showed indolent Non-Hodgkin's Lymphoma, 25% (N=13) were atypical, and 11.5% (N=6) were reactive. All lymph nodes with indolent NHL were of MZL subtype. Compared to wild type (n=3), the new CD19-Cre-PTENfl/fl -LKB1fl/fl (n=3) showed an overall increase in spleen mass (120 vs 196 mg, p=0.0564), % B1 cells (4% vs 59%, p= 0.0075), % MZ cells (5% vs 30%, p=0.0547), % plasma cells (1% vs 12%, p=0.0729), and decrease in % FO cells (80% vs 12%, p=0.0003) by flowcytometry. Further characterization of the new model is currently underway. Conclusion: Marginal zone lymphoma remains an incurable lymphoma that lacks reliable preclinical models. Our data provides, for the first time, a proof of concept on the role of the PI3K-mTOR pathway in the pathogenesis of marginal zone lymphoma and paves the way for future studies understanding the biology of this disease, and developing rational therapies for this incurable malignancy. Disclosures Yazbeck: Celgene: Consultancy; AstraZeneca: Consultancy; Gilead: Research Funding; Seattle Genetics: Consultancy; Verastem: Speakers Bureau.

scholarly journals Induction of proliferation and blast transformation by interferon in human malignant and non-malignant lymph node B cells

Blood ◽  
1989 ◽  
Vol 73 (8) ◽  
pp. 2171-2181 ◽  
Author(s):  
L Ostlund ◽  
P Biberfeld ◽  
KH Robert ◽  
B Christensson ◽  
S Einhorn
Keyword(s):  
Lymph Node ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Blood Cells ◽  
Blast Transformation ◽  
B Cell Lymphomas ◽  
Lymph Node Cells ◽  
Malignant Lymph Nodes ◽  
In Cells

Abstract The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compared with effects on mononuclear blood cells from chronic lymphocytic leukemia (CLL) patients and healthy donors. Natural IFN-alpha (nIFN-alpha) induced a proliferative response in cells from seven of 17 of the B-cell lymphomas, in two of eight of the non-malignant lymph nodes, and in lymphoid blood cells from two of 32 CLL patients. With few exceptions, the proliferating cells were B cells and the data suggest that IFN acts directly on the B cells. Proliferation was not induced with IFN in cells from the T-cell lymphoma or in mononuclear blood cells from 13 healthy donors. nIFN-alpha induced blast transformation in cells from ten of 14 of the B-cell lymphomas and in four of seven of the non- malignant lymph nodes. Also beta- and gamma-IFN were shown to induce proliferation and blast transformation in lymph node cells from some patients. No major effect on the expression of various differentiation markers could be observed following culture in the presence of nIFN- alpha. We conclude that IFNs can induce proliferation and blast transformation in malignant and non-malignant B cells from lymph nodes.

scholarly journals Histomorphometric Study of Axillary Lymph Nodes in Different Age Groups

2019 ◽  
Vol 08 (04) ◽  
pp. 136-141
Author(s):  
Kafeel Hussain A. ◽  
Shaweez Fathima S. ◽  
V. Sathialakshmi
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Germinal Centers ◽  
Axillary Lymph Nodes ◽  
Strong Impact ◽  
Axillary Lymph ◽  
Cross Sectional ◽  
Age Related

Abstract Background Although some age-related changes in lymph node histoarchitecture have been described, they are seldom taken into account in traditional depictions of lymph nodes. Recently introduced clinical procedures, such as intranodal vaccinations have demonstrated the need for an accurate knowledge of the degenerative processes of lymph nodes. It is thus deemed necessary to obtain a detailed insight into anatomical changes within the lymph node throughout life as age-related degeneration can have a strong impact on the outcome of these new therapeutic strategies. Aim To study the size and shape of the lymph nodes and to establish the age-dependent histoarchitectural changes in the lymph nodes in different age groups. Materials and Methods A cross-sectional study was conducted in a total of 35 axillary lymph nodes. The adult axillary group of lymph nodes were from subjects aged between 18 and 70 years. The fetal lymph nodes were collected from 8 stillborn fetuses between 37 and 42 weeks. Thickness of the cortex and diameter of the germinal centers were measured using ocular and stage micrometer. Results None of the fetal lymphocytic follicles showed evidence of a prominent germinal center. The germinal centers of young adults were not only more numerous but also larger in size when compared with the old. An age-related involution of the paracortical region was witnessed in the axillary lymph nodes. No evidence of lipomatous atrophy was encountered in any of the fetal lymph nodes. Interesting evidence of it was encountered in younger age groups. However, this was the most prominent feature in the older groups.

A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival

2010 ◽  
Vol 189 (1) ◽  
pp. i1-i1
Author(s):  
Robert B. Henderson ◽  
Katarzyna Grys ◽  
Anne Vehlow ◽  
Carine de Bettignies ◽  
Agnieszka Zachacz ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Survival ◽  
Cell Development ◽  
B Cell Development ◽  
White Pulp ◽  
Splenic White Pulp
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