Migratory cues controlling B‐lymphocyte trafficking in human lymph nodes

2020 ◽  
Vol 99 (1) ◽  
pp. 49-64
Author(s):  
Saem Mul Park ◽  
Anna ES Brooks ◽  
Chun‐Jen J Chen ◽  
Hilary M Sheppard ◽  
Evert Jan Loef ◽  
...  

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 978-989 ◽  
Author(s):  
Chung Park ◽  
Il-Young Hwang ◽  
Rajesh K. Sinha ◽  
Olena Kamenyeva ◽  
Michael D. Davis ◽  
...  

Abstract B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs.



1988 ◽  
Vol 16 (4) ◽  
pp. 143-145 ◽  
Author(s):  
LUCAS L. COLOMBO ◽  
MARÍA DEL C. LÓPEZ ◽  
JORGE HERKOVITS ◽  
MARÍA E. ROUX


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-51-SCI-51
Author(s):  
Thorsten R. Mempel

Abstract Abstract SCI-51 Lymph nodes provide specialized stromal environments that support the maintenance and homeostasis of T and B lymphocyte populations and are also staging grounds for lymphocyte effector responses against pathogens and transformed cells. They serve as immune information hotspots by collecting lymph fluid from peripheral tissues, especially our external and internal epithelial body surfaces, thus displaying a condensed representation of foreign and self-antigens at these sites in addition to integrating innate alarm signals that report tissue damage or pathogen invasion. Naïve B and T cells constantly traffic through these environments via the blood stream and efferent lymphatic vessels, which allows for efficient matching of their antigen receptor repertoires with the regional antigenic landscape. Depending on the absence or presence of signs of a potential threat to the organism, the result may be either tolerance or immunity towards the origin of these antigens. The architecture of lymph nodes is optimized to facilitate the presentation of lymph-borne antigen in various forms and to guide naïve lymphocytes in their search for 'their' cognate antigen in the form in which they are able to 'see' it. It also facilitates the cellular crosstalk with other immune cell populations that shape and regulate an ensuing adaptive response if cognate antigen is encountered in an immunogenic context. Our conception of how these various tasks are accomplished has recently been enriched through new methodological approaches that include the dynamic in situ or in vivo visualization of cellular and molecular processes using modern microscopy technology. We will review some recent insights into the function of lymph nodes derived from these studies. Disclosures No relevant conflicts of interest to declare.



Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5393-5393 ◽  
Author(s):  
Weihong Chen ◽  
Xin Du ◽  
Changru Luo ◽  
Qiaoxia Zhang ◽  
Mingjun Wang

Abstract BACKGROUND: Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma(NHL), an aggressive lymphoma that does not respond well to chemotherapy. The patient has chemotherapy-refractory MCL. As the patient immunophenotype is CD19 positive, anti-CD19 Chimeric Antigen Receptor (CAR T 19) Cells are administered in order to treat his chemotherapy-refractory MCL. CASE PRESENTATION: The MCL patient, who is male and 60 years of age, has been treated at Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University. Patient had been suffering from painless enlarged lymph nodes on neck, armpits and groin for two years when he was hospitalized in April 2015; he also suffered from abdominal pain since March 2015 and shortness of breath for 7 days. Physical examination: the painless enlarged lymph nodes on neck, armpits and groin from multiple bilateral, 1 × 1.5-4.5 × 5cm size. Right groin lymph node biopsy and immunohistochemistry showed NHL, B lymphocyte cell type, MCL. Bone marrow showed 7% of lymphoma cells. Immunophenotype showed positive expressions of CD5, CD19, CD20, CD23. PET/CT scan showed systemic lymph node with multiple nodules and massively increased images, with diffusion and radioactivity in the spleen having also increased. CT showed right pleural effusion a lot, hilar, chunks of retroperitoneal tumor, splenomegaly. Diagnosis was MCL IV of Group B, B lymphocyte cell type with right pleural effusion. We treated the patient with R-CHOP 4 cycles of chemotherapy from May 7, 2015. The result was poor. We infused autologous T cells transduced with a CAR T 19 cells retroviral vector with the chemotherapy-refractory MCL at doses of 6.0×10e8 CAR T 19 cells October, 2015. Patients were monitored for a response, any toxic effects, and the expansion and persistence of circulating CAR T 19 cells. After CAR T 19 cells were infused, the patient experienced chills, fever, shortness of breath, abdominal distension, abdominal pain, chest tightness, and heart palpitations for 9 days. The diagnosis was cytokine release syndrome. After the patient took an anti-IL-6R antibody, he began to recover. Enlarged lymph nodes got shrunken after being infused with CAR T19 cells for 7 days. The peripheral blood CD19 B lymphocytes cell is 0. The right pleural effusion gradually decreased. The lymphadenopathy was cured after 4 months of infusion, with pleural effusion disappearing after 5 months. Q-PCR was used to detect the amount of CAR T 19 cells, which stood at 1.68x10e6 copies/L after 6 months of infusion. After treatment with CAR T 19 cell therapy for 10 months, the patient's state is good. CONCLUSIONS: Cancer immunotherapy as a method of cancer treatment is the most effective after conventional treatments such as radiotherapy, chemotherapy, and surgery. For CD19+ lymphoma, CD19 is a very favorable target, because the expression of CD19 is limited to B cells and not expressed in other tissues or cells. Currently, the efficacy of this treatment in treating MCL remains to be seen. Effects of chemotherapy on the patient's MCL is negligible, due to the fact that his lymph nodes and lymph tissue have become malignant. As a result we chose the CAR T19 cell therapy genetic engineering technique as a method of treatment, to which the patient has responded well. Disclosures No relevant conflicts of interest to declare.



2018 ◽  
Vol 9 (4) ◽  
pp. 976-987 ◽  
Author(s):  
Luïse Robbertse ◽  
Sabine Annette Richards ◽  
Sarah Jane Clift ◽  
Annette-Christi Barnard ◽  
Andrew Leisewitz ◽  
...  


Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2330-2340 ◽  
Author(s):  
Mee Rhan Kim ◽  
Raffi Manoukian ◽  
Richard Yeh ◽  
Scott M. Silbiger ◽  
Dimitry M. Danilenko ◽  
...  

We have identified and cloned a novel human cytokine with homology to cytokines of the interleukin-17 (IL-17) family, which we have termed human IL-17E (hIL-17E). With the identification of several IL-17 family members, it is critical to understand the in vivo function of these molecules. We have generated transgenic mice overexpressing hIL-17E using an apolipoprotein E (ApoE) hepatic promoter. These mice displayed changes in the peripheral blood, particularly, a 3-fold increase in total leukocytes consisting of increases in eosinophils, lymphocytes, and neutrophils. Splenomegaly and lymphoadenopathy were predominant and included marked eosinophil infiltrates and lymphoid hyperplasia. CCR3+ eosinophils increased in the blood and lymph nodes of the transgenic mice by 50- and 300-fold, respectively. Eosinophils also increased 8- to 18-fold in the bone marrow and spleen, respectively. In the bone marrow, most of the eosinophils had an immature appearance. CD19+ B cells increased 2- to 5-fold in the peripheral blood, 2-fold in the spleen, and 10-fold in the lymph nodes of transgenic mice, whereas CD4+ T lymphocytes increased 2-fold in both blood and spleen. High serum levels of the cytokines IL-2, IL-4, IL-5, granulocyte colony-stimulating factor, eotaxin, and interferon γ were observed. Consistent with B-lymphocyte increases, serum immunoglobulin (Ig) M, IgG, and IgE were significantly elevated. Antigenic challenge of the transgenic mice with keyhole limpet hemocyanin (KLH) resulted in a decrease in anti-KLH IgG accompanied by increases of anti-KLH IgA and IgE. In situ hybridization of transgenic tissues revealed that IL-17Rh1 (IL-17BR/Evi27), a receptor that binds IL-17E, is up-regulated. Taken together, these data indicate that IL-17E regulates hematopoietic and immune functions, stimulating the development of eosinophils and B lymphocytes. The fact that hIL-17E overexpression results in high levels of circulating eosinophils, IL-4, IL-5, eotaxin, and IgE suggests that IL-17E may be a proinflammatory cytokine favoring Th2-type immune responses.



Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5907-5918 ◽  
Author(s):  
Eugenia Manevich-Mendelson ◽  
Valentin Grabovsky ◽  
Sara W. Feigelson ◽  
Guy Cinamon ◽  
Yael Gore ◽  
...  

Abstract Talin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.



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