Immunological studies on PD-1-deficient mice: implication of PD-1 as a negative regulator for B cell responses
Immunological studies on PD-1-deficient mice: implication of PD-1 as a negative regulator for B cell responses
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DOI：
10.1093/intimm/10.10.1563
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发表时间：
1998-10-01
影响因子：
4.4
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Nishimura, H;Minato, N;Honjo, T
PD-1是一个IG超家族成员，在胞质尾区含有一个基于免疫受体酪氨酸的抑制基序，它在一小部分CD 4（-）CD 8（-）正常胸腺细胞中表达，并在活化后在外周淋巴细胞中诱导表达。为了评估PD-1在免疫应答中的可能作用，通过基因靶向策略产生PD-1缺陷（PD-1（-/-））小鼠。PD-1（-/-）小鼠发育和生长正常。尽管胸腺明显正常，但PD-1（-/-）小鼠显示中度但一致的脾肿大，这反映了淋巴细胞和骨髓细胞的细胞构成增加。与对照同窝小鼠相比，PD-1（-/-）小鼠中抗IgM抗体引起的a细胞增殖反应增强，但抗CD 3（145- 2C 11）mAb引起的T细胞增殖反应未增强。PD-1（-/-）小鼠显示IgG 2b、伊加和最显著的IgG 3的血清水平增加，而IgM和IgG 1的血清水平与对照小鼠相当。此外，PD-1（-/-）小鼠对2型T非依赖性抗原DNP-Ficoll的IgG 3抗DNP抗体应答显著增强，IgM和IgG 1抗体应答与同窝对照相当。在腹膜腔中，PD-1（-/-）小鼠中的B-1细胞群显示出CD 5（B-1细胞活化的负调节因子）表达显著降低，尽管B-1细胞数量略有增加。因此，PD-1被认为参与细胞增殖和分化的特定方面的负调节，包括类别转换。
PD-1, an Ig superfamily member, contains an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail, It is expressed in a minor fraction of CD4(-)CD8(-) normal thymocytes and induced in peripheral lymphocytes following activation. To assess the possible roles of PD-1 in the immune responses, PD-1-deficient (PD-1(-/-)) mice were generated by a gene-targeting strategy. PD-1(-/-) mice developed and grew normally. Although the thymus was apparently normal, PD-1(-/-) mice showed moderate but consistent splenomegaly, which reflected the increased cellularity of both lymphoid and myeloid cells. The proliferative response of a cells by anti-IgM antibodies, but not of T cells by an anti-CD3 (145-2C11) mAb in vitro, was augmented in PD-1(-/-) mice as compared with control littermates. PD-1(-/-) mice showed increased serum levels of IgG2b, IgA and most strikingly IgG3, while those of IgM and IgG1 were comparable with control mice. Furthermore, PD-1(-/-) mice exhibited significantly augmented IgG3 anti-DNP antibody response to a type 2 T-independent antigen, DNP-Ficoll, with comparable IgM and IgG1 antibody responses with littermate controls. In the peritoneal cavity, the B-1 cell population in PD-1(-/-) mice exhibited significantly reduced expression of CD5, a negative regulator of B-1 cell activation, despite a marginal increase in the number of B-1 cells. Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of a cell proliferation and differentiation including class switching.