Kim Cheol Joo, Hara Eri, Shimizu Akira, Sugai Manabu, Kimura Shunsaku
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.
J Pharm Sci. 2015 May;104(5):1839-47. doi: 10.1002/jps.24397. Epub 2015 Feb 26.
A polymeric micelle (Lactosome) composed of amphiphilic polydepsipeptide, poly(sarcosine)-block-poly(L-lactic acid), was reported as a T cell-independent antigen. We show here that Lactosome-responsive B cells are predominantly found in the peritoneal cavity (PerC). After immunization of mice with Lactosome, antibody-secreting cells (ASCs) are found only in spleen and bone marrow (BM), but not in PerC. The enzyme-linked immunospot assay shows that the dominant ASCs are plasmablasts in spleen. 5-Bromo-2'-deoxyuridine (BrdU) assay reveals that Lactosome-responsive peritoneal B1a cells proliferate by the stimulation of Lactosome and the majority of them stay there. These data indicate that the primary site for Lactosome to interact with B cells is in PerC, and some of activated B cells migrate into spleen or BM and differentiate into plasmablast there. As expected, when the B1a cells in PerC are collected from the Lactosome-immunized mice and are transplanted into recombination activating gene 2 (RAG2)(-/-) mice, the anti-Lactosome immunoglobulin M (IgM) production is observed in the recipient mice. It is therefore considered that the peritoneal B1a cells stimulated by Lactosome are the source of the sustained plasmablasts in spleen.
一种由两亲性聚缩肽聚（肌氨酸）-嵌段-聚（L-乳酸）组成的聚合物胶束（脂质体）被报道为一种非T细胞依赖性抗原。我们在此表明，对脂质体有反应的B细胞主要存在于腹腔（PerC）中。在用脂质体免疫小鼠后，仅在脾脏和骨髓（BM）中发现抗体分泌细胞（ASC），而在腹腔中未发现。酶联免疫斑点试验表明，脾脏中占主导地位的ASC是浆母细胞。5-溴-2'-脱氧尿苷（BrdU）试验显示，对脂质体有反应的腹腔B1a细胞通过脂质体的刺激而增殖，并且它们中的大多数留在那里。这些数据表明，脂质体与B细胞相互作用的主要部位在腹腔，一些活化的B细胞迁移到脾脏或骨髓并在那里分化为浆母细胞。正如预期的那样，当从用脂质体免疫的小鼠中收集腹腔中的B1a细胞并将其移植到重组激活基因2（RAG2）（-/-）小鼠中时，在受体小鼠中观察到抗脂质体免疫球蛋白M（IgM）的产生。因此，认为受脂质体刺激的腹腔B1a细胞是脾脏中持续存在的浆母细胞的来源。
