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We investigated the <jats:italic>in situ<\/jats:italic> distribution of cells producing lymphotoxin\u2010beta (<jats:italic>LTB<\/jats:italic>), lymphotoxin\u2010alpha (<jats:italic>LTA<\/jats:italic>), and tumour necrosis factor\u2010alpha (<jats:italic>TNFA<\/jats:italic>) transcripts in human reactive lymph nodes and in follicular lymphomas with follicular or diffuse growth pattern. <jats:italic>LTB<\/jats:italic> was the cytokine most abundantly produced in germinal centres. <jats:italic>LTB<\/jats:italic> was present in nearly 90% of germinal centre cells whereas <jats:italic>LTA<\/jats:italic> and <jats:italic>TNFA<\/jats:italic> were detected in 30 and 50%, respectively. Moreover, the amount of <jats:italic>LTB<\/jats:italic> expressed in reactive germinal centre cells was 80\u2010fold higher than that of <jats:italic>LTA<\/jats:italic> and 20\u2010fold higher than that of <jats:italic>TNFA<\/jats:italic>. <jats:italic>LTB<\/jats:italic>\u2010positive cells were more numerous in the germinal centre dark zone, whereas expression of the FDC proteins CD21, CD23, VCAM, and CXCL13 was more intense in the light zone. Tumour cells of follicular lymphomas produced less <jats:italic>LTB<\/jats:italic> than reactive germinal centre cells. The results of the <jats:italic>in situ<\/jats:italic> study were confirmed by RT\u2010PCR; <jats:italic>LTB<\/jats:italic> was significantly more abundant in reactive lymph nodes than in follicular lymphoma, with the lowest values detected in predominantly diffuse follicular lymphoma. In neoplastic follicles, low production of <jats:italic>LTB<\/jats:italic> by tumour B cells was associated with weaker expression of CD21+\/CD23+ by FDCs. Our findings detail for the first time the distribution of <jats:italic>LTA<\/jats:italic>\u2010, <jats:italic>LTB<\/jats:italic>\u2010, and <jats:italic>TNFA<\/jats:italic>\u2010producing cells in human reactive germinal centres and in follicular lymphoma. They suggest the possibility that impaired tumour\u2010cell <jats:italic>LTB<\/jats:italic> production may represent a determinant of FDC phenotype loss and for defective follicular organization in follicular lymphoma.<\/jats:p>","DOI":"10.1002\/cjp2.97","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T17:42:50Z","timestamp":1516815770000},"page":"124-134","source":"Crossref","is-referenced-by-count":21,"title":["Reduced lymphotoxin\u2010beta production by tumour cells is associated with loss of follicular dendritic cell phenotype and diffuse growth in follicular lymphoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Giuseppina","family":"Pepe","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Clinical and Molecular Medicine Sapienza University, Sant'Andrea Hospital Rome 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