Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and neoplastic follicles involves very late antigen-4 and vascular cell adhesion molecule-1

Freedman, AS; Munro, J M; Morimoto, Chieko; McIntyre, BW; Rhynhart, Kurt K.; Lee, N; Nadler, LM

doi:10.1182/blood.v79.1.206.bloodjournal791206

Cited by 12 publications

(15 citation statements)

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“…Meredith et al (1993) demonstrated that primary endothelial cells undergo apoptosis when denied integrin-dependent adhesion to extracellular matrix. Integrins and particularly VLA-4 have been shown to participate in the binding of follicular lymphoma cells to VCAM-1 expressed on dendritic cells in lymph-node sections (Freedman et al, 1992). Integrins also mediate the adhesion of cells to extracellular matrix proteins, which play a vital role in haemopoiesis (Long et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro

et al. 1996

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Leukaemic cells from most cases of B-chronic lymphocytic leukaemia die rapidly by apoptosis in vitro unless they are cultured in the presence of interleukin-4 or interferon alpha or gamma. We now report prolonged survival of purified CLL cells cultured on bone marrow (BM) derived stromal cells in the absence of exogenous growth factors. In 10 cases of CLL examined 0-61% (mean 14.7%) of the cells were viable after 10 d culture in medium alone, whereas in the presence of BM stromal cells 10-102% (mean 47.0%) of cells were recovered alive (P < 0.005) in 7/10 cases of CLL, cells remained viable after 30 d of culture in BM stromal cells with cell recovery of 12-65%. These long-term cultured CLL cells were Epstein Barr virus negative, shown by the failure to detect the ENBA-2 and BZLF1 genes of EBV by PCR analysis. Identity between day 0 and day 30 CLL cells was demonstrated by sequence analysis of their clonal IgH CDR3 region. Adherence of CLL cells to BM stromal cell layers was critical for their protection from apoptosis. Separation of CLL cells from stroma by 0.45 micron culture filters resulted in loss of the protective effect of the stromal cells. Stromal cells were also able to protect CLL cells from hydrocortisone-induced apoptotic cell death. Our findings provide an in vitro system that can be used to analyse the growth requirements of CLL cells and their chemosensitivity in an in vitro environment that mimics the in vivo milieu.

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Section: Discussionmentioning

confidence: 99%

Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro

et al. 1996

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“…In previous studies, this device was helpful to explain the adherence of leukocytes to high endothelial venules (28,29) and to describe the adhesion orb cells to the germinal centers (20,37,38). Adhesion of B cells to germinal centers of lymphoid follicles, for example, was found to be mediated by tx4~l on the B cell surface and by VCAM-1 expressed on FDCs (20,37). Since not all cell lines that were positive for e~4~1 bound to the germinal center, the existence of other cellular structures that mediate this adhesion was postulated.…”

Section: Discussionmentioning

confidence: 99%

Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin.

Behr

Schriever

1995

The Journal of Experimental Medicine

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SummaryAdhesion ofB lymphocytes within the different compartments of secondary lymphoid organs is essential for the function of the humoral immune response. It is not currently known how the temporary immobilization orb cells in distinct areas of this complex microenvironment is regulated. The present study aimed at defining B cell antigens that initiate binding of B cells to human tonsil sections in situ. Engaging the B cell antigens CD19 and target of an antiprohferative antibody 1 (TAPA-1) with monoclonal antibodies induced adhesion of these B cells to the interfollicular stroma. This binding occurred through the integrin o~4131 on the B cell surface and via the extracellular matrix protein fibronectin expressed in the interfollicular compartment of the tonsil. Signaling through either antigen, CD19 or TAPA-1, depended on tyrosine kinases. Binding induced by engaging CD19 required an intact cytoskeleton, whereas TAPA-l-transmitted adhesion did not. We suggest that CD19 and TAPA-1 have a novel and unique function by regulating an o~4[31/fibronectin-mediated binding of B cells to the interfollicular stroma of lymphoid tissues.

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“…The majority of human follicular lymphomas are believed to originate from germinal centre B cells and start as B cell tumours of low malignancy [16,17]. They have a tendency to become aggressive during the later stages of the disease, usually several years after the onset of the lymphoma [18].…”

Section: Introductionmentioning

confidence: 99%

The Somatic Hypermutation Activity of a Follicular Lymphoma Links to Large Insertions and Deletions of Immunoglobulin Genes

Kaartinen

1995

Scand J Immunol

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A biopsy specimen from a patient with follicular lymphoma was divided into two fragments. DNA was extracted from one fragment and a 1.2 kb region of the functional heavy chain (IgH) gene was amplified, cloned and sequenced (eight clones). From the other fragment a cell line (HF-1) was started. The IgH gene region was amplified from the cell line, and sequenced without cloning. The nine sequences obtained could be arranged into a genealogical tree where the individual sequences differed from the deduced ancestor by 16-29 single nucleotide changes, some also by an insertion and/or a deletion. It is apparent that the sequence alterations were caused by somatic mutations during the growth of the lymphoma. The comparison of the sequences with two published (allelic) germline sequences of the human JH region showed approximately 20% non-homology. The differences included five additional multinucleotide insertion/deletion changes, the longest of them a 101-nucleotide insertion. Two long insertions were homologous to the adjacent germline sequences. We propose that most of the changes observed, including long deletions and insertions, represent or are linked to somatic hypermutation events of the Ig gene type. Although in a few cases large deletions and insertions (> 2 bp) have been found in mutated immunoglobulin genes, our results, for the first time, firmly link these deletions/insertions to somatic hypermutations; their frequency was found to be 2.2% of the observed mutational events in the non-translated gene regions. HF-1 is the first follicular lymphoma line successfully established from a lymphoma known to have hypermutated its Ig genes during the malignant growth. It is a candidate cell line to be studied for its ability to generate mutations of B cell type in cell cultures.

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Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and neoplastic follicles involves very late antigen-4 and vascular cell adhesion molecule-1

Cited by 12 publications

References 0 publications

Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro

Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro

Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin.

The Somatic Hypermutation Activity of a Follicular Lymphoma Links to Large Insertions and Deletions of Immunoglobulin Genes

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