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.
Pistoia
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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