Hema-Quebec's Department of Research and Development, 1070 Avenue des Sciences-de-la-Vie, Québec, QC, Canada G1V 5C3; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, 1045 Avenue de la Médecine, Québec, QC, Canada G1V 0A6.
J Immunol Res. 2016;2016:7801781. doi: 10.1155/2016/7801781. Epub 2016 Oct 31.
The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival. We tested low oxygen concentrations and coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all cultures were performed using an animal protein-free medium. Overall, our model enables the generation of high proportions of CD38CD138CD31 plasma cells (≥50%) when CD40-activated switched memory B lymphocytes were cultured in direct contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12 and TGF-, usually found in the bone marrow, was linked to the presence of MSC. The level of oxygen appeared less impactful than the contact with MSC. This study shows for the first time that expanded switched memory B lymphocytes can be differentiated into plasma cells using exclusively a serum-free medium.
人类 B 淋巴细胞分化为浆细胞是适应性免疫中最令人关注的问题之一。然而，浆细胞的终末分化和存活仍然有很多有待发现的地方，特别是在针对已转换的记忆 B 淋巴细胞时。浆细胞可以响应 CXCL12 梯度迁移到骨髓中，并在分泌抗体的同时存活数年。在本研究中，我们旨在更深入地了解有利于浆细胞存活的龛位。我们测试了低氧浓度和与人骨髓间充质干细胞（MSC）的共培养。此外，所有培养均在无动物蛋白的培养基中进行。总的来说，当 CD40 激活的已转换的记忆 B 淋巴细胞与间充质干细胞直接接触时，我们的模型能够产生高比例的 CD38CD138CD31 浆细胞（≥50%）。在这些培养物中，通常在骨髓中发现的 CXCL12 和 TGF-β的分泌与 MSC 的存在有关。氧气水平的影响似乎不如与 MSC 的接触大。本研究首次表明，仅使用无血清培养基就可以将扩增的已转换的记忆 B 淋巴细胞分化为浆细胞。
