Relationships between B cell cytokine production in secondary lymphoid follicles and apoptosis of germinal center B lymphocytes.
In vivo or in vitro activated human B lymphocytes can produce a wide spectrum of cytokines which are involved in the regulation of hematopoiesis and of the inflammatory and immune responses. Three major B cell subsets have been identified in peripheral lymphoid organs: the germinal center (GC), the mantle zone (MZ) and the marginal zone B lymphocytes. GC and MZ B cells can be isolated as CD39- surface (s)IgD- or CD39+ sIgD+ cells, respectively. Therefore, it is now possible to investigate the cytokine producing potential of purified GC and MZ B lymphocytes. In this article, the optimal conditions for the assessment of cytokine production by human B cells are first discussed; thereafter, the spectrum of B lymphocyte-derived cytokines is described together with their possible physiological meaning. Next, data concerning the cytokines released in vitro by either GC or MZ B cells are presented. Some cytokines, such as granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF), are produced only by GC or MZ B lymphocytes, respectively, whereas other cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) or IL-10 are synthesized by both B cell subsets. Finally, the relationships between B cell-derived cytokines and apoptosis of GC B lymphocytes are discussed, and a hypothetical model of the cytokine networks in secondary lymphoid follicles is presented. It is expected that these notions will help to clarify the pathophysiology of lymphoproliferative and autoimmune diseases.
Laboratory of Oncology, Scientific Institute G. Gaslini, Genova, Italy.
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D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D016207:Cytokines / Q000096:biosynthesis*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008213:Lymphocyte Activation; D018448:Models, Immunological; D014066:Palatine Tonsil
D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor