Fibroblasts enhance the in vitro survival of human memory and naïve B cells by maintaining intracellular levels of glutathione.
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.
Jeong
Euh Jun
EJ
Department of Microbiology and Immunology, Kangwon National University College of Medicine, and Vascular System Research Center, Kangwon National University, Chunchon 200-701, Korea.
Lee
In Yong
IY
Choi
Jin-Suk
JS
Cheon
In Su
IS
Kang
Gu
G
Choe
Jongseon
J
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
D016207:Cytokines; D005978:Glutathione