title: Fibroblasts enhance the in vitro survival of human memory and naïve B cells by maintaining intracellular levels of glutathione.
abstract: To gain insight into the mechanism of memory B cell survival, we cultured highly purified subpopulations of tonsillar B cells with tonsillar fibroblasts. The fibroblasts greatly enhanced the survival of memory and naïve B cells but did not delay the rapid apoptosis of germinal center B cells. B cell activation was not observed during the period of culture, as shown by the absence of activation markers and of cycling cells. These findings were reproduced when the B cells were physically separated from the fibroblasts by a semi-permeable transwell-membrane, indicating that the survival factor(s) were diffusible. Several cytokines including IL-6, IL-15, and VEGF were tested for survival activity but none could replace the fibroblasts. However, the addition of reduced glutathione (GSH) to the naïve and memory B cells significantly enhanced their survival, and depletion of GSH resulted in rapid loss of B cell viability. Furthermore, intracellular glutathione levels were maintained when the B cells were co-cultured with fibroblasts. Our results suggest that glutathione plays an important role in the survival of memory and naïve B cells in the presence of stromal cells.
authors.affiliation: Department of Microbiology and Immunology, Kangwon National University College of Medicine, and Vascular System Research Center, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Euh Jun
authors.initials: EJ
authors.lastname: Jeong
authors.forename: In Yong
authors.initials: IY
authors.lastname: Lee
authors.forename: Jin-Suk
authors.initials: JS
authors.lastname: Choi
authors.forename: In Su
authors.initials: IS
authors.lastname: Cheon
authors.forename: Gu
authors.initials: G
authors.lastname: Kang
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
mesh_terms: D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D018858:Germinal Center / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil / Q000378:metabolism
chemical_list: D016207:Cytokines; D005978:Glutathione