Role of lupus murine B cells in abnormal development of T cell subsets

Abstract

Objective To study the effects of B cells from lupus prone Triple congenic (TC) mouse model on the differentiation and development of T cell subsets. Methods The spleen size and B cell numbers were measured, and surface CD40, CD86 and Ⅰ-Ab molecules on B cells as well as CD4+ T cell subsets were detected using flow cytometry when the spontaneous systemic lupus erythematosus (SLE) model TC mice and control B6 mice were 6 months old. In addition, the chimera of TC B cells and B6 CD4+T cells or chimera of B6 B cells and B6 CD4+ T cells were transferred into B6.Rag-/- mice via intravenous injection. Then, T cell subsets in the spleen of recipient B6.Rag-/- mice were observed 7 days after cell transplantation. Results TC mice had significantly bigger spleen [(5 337±934) mg] and more CD19+ B cell number [(276.0±48.7)×107] than control B6 mice [spleen weight: (91±4) mg; B cell number: (6.4±0.3)×107](P 0.05). The recipient B6.Rag-/- mice transplanted with TC B cells had significantly more Th1 subset [(54.1±2.8)%] and IL-21+CD4+ T cell population [(14.3±1.0)%], but less Th17 subset [(2.05±0.09)%] in spleen than the recipient B6.Rag-/- mice administered by B6 B cells [Th1 subset: (39.5±1.1)%; IL-21+CD4+T cell population: (7.5±1.2)%; Th17 subset: (6.45±1.10)%](P<0.01). Conclusion The B cells of lupus-prone TC mice exhibit a markedly hyper-activation in spleen, and promote CD4+ T cells differentiation preferentially into Th1 subset and IL-21+CD4+ T cell population, which may further contribute to SLE pathogenesis. Key words: Lupus erythematosus, systemic; Mouse model; Receptors, antigen, B-cell; T-lymphocyte cell subsets; Differentiation