Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS) suppresses terminal differentiation and high-rate Ig secretion with no effect on proliferation. As shown here, different B cell populations show characteristic mean values of ligand concentration required for 50% inhibition, with Gaussian distributions of sensitivity to IgM receptor ligation that reflect cellular heterogeneity of 'al-or-none' inhibitions in single cells. Differential sensitivity of B cell populations to IgM ligation seems to be locally determined by the cellular environment and unrelated to the 'maturity' of the responding cells. Thus, while long-lived peritoneal B cells are 3- to 5-fold more resistant than splenic B cells, there is no difference in sensitivity between short- and long-lived B cells in the spleen. Furthermore, while B cells in bone marrow and spleen differ in sensitivity by two orders of magnitude, B cells differentiated in vitro from bone marrow pre-B cells are as resistant as splenic B cells. Moreover, bone marrow cell culture supernatants restore a high level of sensitivity in such cell populations. Differential sensitivity to IgM receptor ligation is reproduced by multivalent nominal antigen, in cell populations that show identical dose-response inhibition curves to direct activation of protein kinase C by phorbol esters. We conclude that the level of sensitivity to IgM ligation is independent of the life span or maturity of the B cell, but differentially regulated in vivo by putative tissue factors.

译文

对脂多糖 (LPS) 响应的b细胞上的表面IgM连接抑制了终末分化和高速度Ig分泌,而对增殖没有影响。如这里所示,不同的b细胞群体显示出50% 抑制所需的配体浓度的特征平均值,其对IgM受体连接的敏感性的高斯分布反映了单细胞中 “al-or-none” 抑制的细胞异质性。B细胞群体对IgM连接的不同敏感性似乎是由细胞环境局部决定的,与响应细胞的 “成熟度” 无关。因此,尽管长寿命的腹膜b细胞的抵抗力比脾b细胞高3至5倍,但脾脏中短寿命b细胞和长寿命b细胞之间的敏感性没有差异。此外,尽管骨髓和脾脏中的b细胞的敏感性相差两个数量级,但从骨髓前b细胞体外分化的b细胞与脾b细胞一样具有抵抗力。此外,骨髓细胞培养上清液在此类细胞群体中恢复了高水平的敏感性。在显示出与佛波酯直接激活蛋白激酶C相同的剂量反应抑制曲线的细胞群体中,多价名义抗原再现了对IgM受体连接的不同敏感性。我们得出的结论是,对IgM连接的敏感性水平与b细胞的寿命或成熟度无关,但在体内受假定的组织因素的差异调节。

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