Original contribution B cells in classical Hodgkin lymphoma are important actors rather than bystanders in the local immune reaction ☆ Christiane S. Tudor MD a , Luitpold V. Distel MD b , Jenny Eckhardt MD, PhD c , Arndt Hartmann MD, PhD d , Gerald Niedobitek MD, PhD e , Maike Buettner MD a, ⁎ a Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany b Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, University Hospital, 91054 Erlangen Germany c Department of Immune Modulation at the Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany d Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany e Institutes of Pathology, Sana Klinikum Lichtenberg/Unfallkrankenhaus Berlin, 10365 Berlin, Germany Received 13 December 2012; revised 4 June 2013; accepted 12 June 2013 Keywords: Classical Hodgkin lymphoma; B cells; Follicular dendritic cell networks; Germinal centers; Plasma cells; Humoral immunity Summary Recent studies, largely focusing on cellular immunity, have demonstrated that the composition of the abundant inflammatory background of Hodgkin lymphoma may affect outcome. This investigation aimed to characterize the potential role of infiltrating B cells and follicular dendritic cell networks in classical Hodgkin lymphoma (cHL) to better assess the role of components of humoral immunity. One hundred two cHL biopsies were investigated by immunohistochemistry with antibodies specific for CD20, CD138, activation-induced cytidine deaminase, and CD21 to characterize B cell distribution and follicular structures. To further subclassify B cells, analyses of tissue microarrays were performed investigating the expression of Mum1, Bcl6, IgD, IgG, IgG4, IgM, T-bet, CD38, CD5, and CD10. For evaluation a computer assisted quantification method was compared with a scoring system. Survival analysis and correlation analysis were performed. The B cell infiltrate was dominated by CD20+ B cells, followed by plasma cells, whereas only few AID+ cells were observed. High numbers of CD21+ follicular dendritic cell networks, CD20+ B cells, IgM+ cells, CD20+ aggregates, and Bcl6+ cells were associated with a better outcome of cHL patients, whereas Pax5+/CD38+ cells had an adverse prognostic impact. Other parameters showed no influence on survival. Our findings suggest that a complex network of B cells is present in the microenvironment of cHL and that B cells might actively contribute to a local anti- as well as pro-tumoral immune response. This indicates that the network of B cells in tumors is probably just as diverse as the T cellular infiltrate and probably functionally as heterogenous. © 2013 Elsevier Inc. All rights reserved. 1. Introduction The immunological reaction in malignant tumors is complex and far from being fully understood. This is particularly true for Hodgkin lymphoma (HL), characterized by a small number of neoplastic Hodgkin and Reed- ☆ The authors declare no conflict of interest. This work was supported by the GRK1071 Viruses of the Immune System of the Deutsche Forschungsgemeinschaft and the ELAN Fond of the University Hospital of Erlangen, Germany. ⁎ Corresponding author. E-mail address: maike.buettner@uk-erlangen.de (M. Buettner). www.elsevier.com/locate/humpath 0046-8177/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humpath.2013.06.006 Human Pathology (2013) xx, xxx–xxx