Long-term functional culture of human tonsil lymphocytes in a three-dimensional bioreactor system (144.32)

Abstract

Abstract Peripheral lymphoid organs are the primary sites of adaptive immune responses, and harbor characteristic anatomical and histological features reflecting separation of cellular subsets (e.g. T and B lymphocytes) and functional compartments. Disruption of lymphoid organ structure by genetic mutations, pharmacological treatments or infection can lead to defective immunity, highlighting the role of tissue organization in immune responses. The generation of in vitro culture systems recapitulating salient features of peripheral lymphoid organs for experimental, biotechnological and clinical applications would be highly desirable, but has so far been hampered by the complexity of these organ systems and has encountered only limited success. We have previously developed a 3D bioreactor system capable of supporting long-term, functional human bone marrow cultures. Here we show that the same system can be adapted for culture of human primary peripheral lymphoid tissue (tonsil) cells for periods up to several weeks in the absence of specific external growth factors or activators. Cells in this system display extended survival, maintain population diversity and phenotypes largely comparable to primary cells, and organize in cellular aggregates with identifiable separation of T and B cell clusters analogous to primary organs. Strikingly, we also show that these cultures are capable of supporting the generation of antibody-producing cells in response to a panel of diverse antigens.