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

响应脂多糖(LPS)的B细胞表面IgM的连接可抑制终末分化和高速率的Ig分泌,而对增殖没有影响。如此处所示,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“异或无”抑制的细胞异质性。 B细胞群体对IgM连接的差异敏感性似乎是由细胞环境局部决定的,并且与响应细胞的“成熟度”无关。因此,虽然长寿腹膜B细胞的抵抗力比脾脏B细胞高3至5倍,但脾脏中短寿和长寿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细胞在敏感性方面相差两个数量级,但体外与骨髓前B细胞分化出的B细胞与脾脏B细胞一样具有抗性。而且,骨髓细胞培养物上清液在这种细胞群体中恢复了高水平的敏感性。在表现出相同剂量反应抑制曲线以直接通过佛波醇酯激活蛋白激酶C的细胞群体中,多价名义抗原重现了对IgM受体连接的不同敏感性。我们得出的结论是,对IgM结扎的敏感性水平与B细胞的寿命或成熟度无关,但在体内受假定的组织因子的调节。

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