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It is currently unclear how the various patterns of deregulation observed in pathology eventually impact the phenotype of malignant B cells and their microenvironment. Follicular lymphoma (FL) is the most common non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells, and its major hallmark is the t(14:18) translocation occurring in B cell progenitors and placing the BCL2 gene under the control of the immunoglobulin heavy chain locus regulatory region (IgH 3\u2032RR), thus exposing it to constitutive expression and hypermutation. Translocation of BCL2 onto Ig light chain genes, BCL2 gene amplification, and other mechanisms yielding BCL2 over-expression are, in contrast, rare in FL and rather promote other types of B-cell lymphoma, leukemia, or multiple myeloma. In order to assess the impact of distinct BCL2 deregulation patterns on B-cell fate, two mouse models were designed that associated BCL2 and its full P1-P2 promoter region to either the IgH 3\u2032RR, within a \u201c3\u2032RR-BCL2\u201d transgene mimicking the situation seen in FL, or an Ig light chain locus context, through knock-in insertion at the Ig\u03ba locus (\u201cIg\u03ba-BCL2\u201d model). While linkage to the IgH 3\u2032 RR mostly yielded expression in GC B-cells, the Ig\u03ba-driven up-regulation culminated in plasmablasts and plasma cells, boosting the plasma cell in-flow and the accumulation of long-lived plasma cells. These data demonstrate that the timing and level of BCL2 deregulation are crucial for the behavior of B cells inside GC, an observation that could strongly impact the lymphomagenesis process triggered by secondary genetic hits.<\/jats:p>","DOI":"10.3390\/cancers14215337","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T23:45:00Z","timestamp":1667087100000},"page":"5337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Distinct B-Cell Specific Transcriptional Contexts of the BCL2 Oncogene Impact Pre-Malignant Development in Mouse Models"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2623-1582","authenticated-orcid":false,"given":"Lina","family":"Zawil","sequence":"first","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-1191","authenticated-orcid":false,"given":"Tiffany","family":"Marchiol","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-5419","authenticated-orcid":false,"given":"Baptiste","family":"Brauge","sequence":"additional","affiliation":[{"name":"UMR U 1236, Univ Rennes 1, INSERM, EFS Bretagne, Equipe Labellis\u00e9e Ligue Contre le Cancer, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Saintamand","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Carrion","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Dessauge","sequence":"additional","affiliation":[{"name":"UMR U 1236, Univ Rennes 1, INSERM, EFS Bretagne, Equipe Labellis\u00e9e Ligue Contre le Cancer, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5502-7735","authenticated-orcid":false,"given":"Christelle","family":"Oblet","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2297-4186","authenticated-orcid":false,"given":"Sandrine","family":"Le Noir","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Mourcin","sequence":"additional","affiliation":[{"name":"UMR U 1236, Univ Rennes 1, INSERM, EFS Bretagne, Equipe Labellis\u00e9e Ligue Contre le Cancer, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myl\u00e8ne","family":"Brousse","sequence":"additional","affiliation":[{"name":"Immunology Department, Faculty of Medicine, Limoges University, Cnrs Umr 7276, Inserm U1262, 2 Rue du Dr Marcland, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco","family":"Derouault","sequence":"additional","affiliation":[{"name":"Chu Dupuytren, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Alizadeh","sequence":"additional","affiliation":[{"name":"UMR U 1236, Univ Rennes 1, INSERM, EFS Bretagne, Equipe Labellis\u00e9e Ligue Contre le Cancer, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolla El","family":"Makhour","sequence":"additional","affiliation":[{"name":"Immunology Department, Science Faculty, Lebanese University, Beirut P.O. 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