Hodgkin's cells express a novel pattern of adhesion molecules

Ellis, P. A.; Hart, Derek N. J.; Colls, B. M.; Nimmo, J. C.; Macdonald, James E.; Angus, Helen

doi:10.1111/j.1365-2249.1992.tb05842.x

Cited by 25 publications

(8 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another scenario might be, that CD11c + B cells, as they differentiate into antibody-secreting cells upon activation ( 13 ), use CR4 during their homing into the bone marrow, where SDF-1 is also expressed ( 31 ). As CD11c is known to be expressed in various B cell malignancies ( 8 , 32 ), it is also very likely, that CR4 has an important role in the pathomechanism of these diseases. Interestingly, in many of these pathological cases CR3 was shown to be expressed together with CR4 ( 8 , 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation

et al. 2020

View full text Add to dashboard Cite

Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) of myeloid cells are known for long to participate in actin linked functions like phagocytosis, adhesion, and migration. The expression and role of these two β 2 -integrins however, in human B lymphocytes have only scarcely been studied so far, although it has been shown recently that CD11c + B cells are mainly memory cells. In our systematic study we investigated B cells isolated from tonsils and peripheral blood of healthy donors. We found, that while only 5% of resting tonsillar B cells expressed CD11c, their number increased up to 26% after 3 days of BCR stimulation. Lower, but still remarkable percentage of B lymphocytes were positive for CD11c after stimulation via TLR9 alone or via TLR9 and BCR simultaneously. At the same time, we detected no significant expression of CD11b on resting or activated tonsillar B cells. Blood B lymphocytes showed a similar expression pattern of both β 2 -integrins. We demonstrated that CD11c molecules appearing on the surface of B cells are newly synthesized, reaching the number of 9,500 per activated B cell. We found that CR4 expressing B cells belong to the memory pool and the increase of CD11c expression on tonsillar B cells upon BCR mediated activation occurs parallel with class switching. Analysis of the function of CD11c revealed, that this β 2 -integrin contributes to the adhesion and migration of activated B lymphocytes. We also demonstrated that the CR4 mediated adhesion promotes the proliferation of the BCR activated cells. Our studies are the first to demonstrate that CD11c expressed on BCR-activated human B cells are not only passive markers but functional drivers of memory B cell responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CD58, also known as lymphocyte function-associated antigen 3, is a glycosylated surface molecule on both B- and T-cells, which provides a stimulatory signal for T cells via the CD2 receptor. The function of CD58 in cHL is two-faced: on the one hand, it is necessary for HRS cells to communicate with CD4-positive T-cells ( 35 ), on the other hand, loss of CD58 expression due to mutations can facilitate immune escape, especially in advanced disease, when HRS cells become less dependent on the surrounding microenvironment ( 36 , 37 ). HLA-G, a non-classical HLA molecule, plays a similar role in cHL and modulates the microenvironment to foster immunotolerance.…”

Section: Hodgkin Lymphoma—the Classical Paradigm For Immunomodulativementioning

confidence: 99%

Mechanisms of Immune Evasion and Immune Modulation by Lymphoma Cells

Menter

Tzankov

2018

Front. Oncol.

View full text Add to dashboard Cite

PurposeTargeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies.MethodsA literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic.ResultsWe elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28. The prototypical example of a lymphoma manipulating and thereby silencing the immune system is Hodgkin lymphoma. Also other lymphomas, e.g., primary mediastinal B-cell lymphoma and some Epstein–Barr virus (EBV)-driven malignancies, use analogous survival strategies, while diffuse large B-cell lymphoma of the activated B-cell type, follicular lymphoma and angioimmunoblastic T-cell lymphoma to name a few, exert further immune escape strategies each. These insights have already led to new treatment opportunities and results of the most important clinical trials based on this concept are briefly summarized. Immune checkpoint inhibition might also have severe side effects; the mechanisms of the rather un(der)recognized hematological side effects of this treatment approach are discussed.ConclusionSilencing the host’s immune system is an important feature of various lymphomas. Achieving a better understanding of distinct pathways of interactions between lymphomas and different immunological microenvironment compounds yields substantial potential for new treatment concepts.

show abstract

“…Amongst others, β 2 -integrins have been also detected on various B cell lymphomas, including diffuse large B-cell lymphoma, mantle cell lymphoma, Hodgkin's lymphoma, CLL or Burkitt's lymphoma [28]. While CR3 and CR4 are reported to appear also on B cells of patients suffering from Hodgkin's lymphoma [12], hairy cell leukaemia [13] or CLL [4,[13][14][15][16][17][18][19], the role of these complement receptors on malignant B cells is still in question. Since CR4 was found to be involved in the adhesion and migration of activated B cells of healthy donors [11], we assumed that it retains its function on malignant B cells and may even serve as an active driver of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Since CD11b and CD11c are known to be expressed by various malignant B cells [4,[12][13][14][15][16][17][18][19], first we tested whether the cells of the EBV-negative Burkitt-like lymphoma line BJAB could serve as a model for examining the role of CR3 or CR4 expressed by malignant human B cells. Flow cytometry measurements revealed that BJAB cells are positive for CD11c, but negative for CD11b (Fig 1A), similarly to the activated B cells of healthy donors [11].…”

Section: Expression and Function Of Cr3 And Cr4 On The B Cell Line Bjabmentioning

confidence: 99%

“…Moreover, these complement receptors have been detected in various B cell malignancies such as in Hodgkin's lymphoma [12], hairy cell leukaemia [13] or chronic lymphocytic leukaemia (CLL) [4,[13][14][15][16][17][18][19]. Out of these CR3 and CR4 bearing B cell malignancies, CLL is the most frequent form of leukaemia in the western world with an age-adjusted incidence of 4.1/100 000.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1

et al. 2021

View full text Add to dashboard Cite

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world. In previous studies, various proportion of patients was found to carry CD11b+ or CD11c+ B cells whose presence was an unfavourable prognostic factor. The exact mechanism however, how these receptors contribute to the pathogenesis of CLL has not been revealed so far. Here we analysed the role of CD11b and CD11c on B cells of CLL patients in the adhesion to fibrinogen and in the migration towards stromal cell derived factor-1 (SDF-1) and studied the role of CR4 in the adherence of the CD11c+ B cell line BJAB. We observed that both CR3 and CR4 mediate adhesion of the malignant B cells. Moreover, we found, that CR4 was strongly involved in the migration of the leukemic cells towards the chemoattractant SDF-1. Our data suggest that CR3 and CR4 are not only passive markers on CLL B cells, but they might contribute to the progression of the disease. Since the role of SDF-1 is prominent in the migration of CLL cells into the bone marrow where their survival is supported, our findings help to understand how the presence of CD11c on leukemic B cells can worsen the prognosis of chronic lymphocytic leukaemia.

show abstract

Hodgkin's cells express a novel pattern of adhesion molecules

Cited by 25 publications

References 32 publications

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation

Mechanisms of Immune Evasion and Immune Modulation by Lymphoma Cells

BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1

Contact Info

Product

Resources

About