Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.
Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.
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DOI：
10.1084/jem.157.2.730
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发表时间：
1983-02-01
期刊：
影响因子：
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通讯作者：
Theofilopoulos AN
中科院分区：
文献类型：
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作者：
Prud'Homme GJ;Park CL;Fieser TM;Kofler R;Dixon FJ;Theofilopoulos AN
自身免疫 MRL/Mp-lpr/lpr 小鼠品系的淋巴结和脾细胞自发产生（在没有促有丝分裂刺激的情况下）诱导 B 细胞分化的因子。该因子不是由缺乏 lpr 基因的同源 MRL/n 小鼠品系或正常小鼠品系产生的。 However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor.尽管该因子作用于静息 B 细胞，但通过使用抗 mu 或脂多糖激活 B 细胞，其效果会大大放大。 MRL/l 小鼠早在 1 个月大时就开始产生该因子，但水平随着年龄和淋巴细胞增殖的出现而增加。细胞耗竭研究表明，该因子是由 Lyt-1+2- 表型的 T 细胞产生的。由于其与 lpr/lpr 基因型相关，我们将这种 B 细胞分化因子称为 L-BCDF。 L-BCDF 的功能分析表明，无论培养物中的细胞密度如何，并且在不存在白细胞介素 2 (IL-2) 的情况下，它都能发挥作用。 In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF 诱导脂多糖激活的 B 细胞中 IgM 和 IgG 的合成；然而，它对 IgG 分泌的影响更大。特别是，在 L-BCDF 存在的情况下，IgG1、IgG2a 和 IgG2b 的产生显着增强。 lpr/lpr 基因型 SLE 小鼠的 T 细胞自发产生 L-BCDF 表明该因子与自身免疫相关。
Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2- phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.