title: hsBAFF regulates proliferation and response in cultured CD4(+) T lymphocytes by upregulation of intracellular free Ca(2+) homeostasis.
abstract: B cell activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, THANK, or zTNF4) is an important survival factor for B cells, and is able to regulate T-cell activation. Recently, we have demonstrated that treatment of mice with human soluble BAFF (hsBAFF) causes a significant increase of percentages of splenic CD4(+) T lymphocytes dose-dependently, but the CD8(+) T lymphocyte percentages maintained unchanged. Here, we show that hsBAFF significantly enhanced CD4(+) T lymphocyte response of cultured mouse splenic cells, and hsBAFF induced the proliferation and IL-2/IFN-γ secretion of purified CD4(+) T lymphocytes suboptimally stimulated through anti-CD3. Of importance, we observed that IL-2 or IFN-γ cytokine has additive effect on the proliferation and activity of hsBAFF-stimulated CD4(+) T lymphocytes. Using Flow cytometry with fluorescent probe, Fluo-3/AM, we found that hsBAFF elicited [Ca(2+)](i) elevation contributing to CD4(+) T cell proliferation. This is evidenced by our finding that pretreatment with BAPTA/AM, an intracellular Ca(2+) chelator, significantly attenuated the proliferation of hsBAFF-stimulated CD4(+) T lymphocytes. Subsequently, we revealed that hsBAFF-stimulated CD4(+) T cell proliferation was markedly suppressed after pretreatment with EGTA, an extracellular Ca(2+) chelator, or with 2-APB, an inhibitor of Ca(2+) influx through CRAC channels, respectively, suggesting that extracellular Ca(2+) influx due to hsBAFF is closely associated with [Ca(2+)](i) elevation contributing to CD4(+) T cell proliferation. In addition, we noticed that hsBAFF-treated cells conferred partial resistance to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca(2+)-ATPase inhibitor. Taken together, our data indicate that hsBAFF may promote CD4(+) T cell proliferation and response by upregulation of [Ca(2+)](i) homeostasis.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wen
authors.forename: Su Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Ma
authors.forename: Shuang Quan
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Long
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D012995:Solubility / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D053264:B-Cell Activating Factor; D015220:Calcium Channels; D007376:Interleukin-2; C505719:TNFSF13B protein, human; D019284:Thapsigargin; D007371:Interferon-gamma; D002118:Calcium