Kennedy Domenick E, Witte Pamela L, Knight Katherine L
Loyola University Chicago, Department of Microbiology and Immunology, USA.
Loyola University Chicago, Department of Microbiology and Immunology, USA.
Dev Comp Immunol. 2016 May;58:30-9. doi: 10.1016/j.dci.2015.11.003. Epub 2015 Nov 11.
B lymphopoiesis is necessary to generate a diverse pool of naïve B cells that are able to respond to a broad spectrum of antigens during immune responses to pathogens and to vaccination. Rabbits have been utilized for many years to generate high affinity monoclonal and polyclonal antibodies. Specific antibodies generated in rabbits have greatly advanced scientific discoveries, but the unique qualities of rabbit B cell development have been underappreciated. Unlike in humans and mice, where B lymphopoiesis declines in mid to late life, B lymphopoiesis in rabbits arrests early in life, between 2 and 4 months of age. This review focuses on the early loss of B cell development in rabbits and the contribution of the bone marrow microenvironment to this process. We also propose directions for future research in this area, and discuss how the rabbit can be used as a model to understand the decline of B lymphopoiesis that occurs in humans late in life. Such studies will be important for developing therapeutics targeted to prevent and/or reverse declining B lymphopoiesis in the elderly, as well as boosting immunity and antibody responses after infection or vaccination.
B淋巴细胞生成对于产生多样化的初始B细胞库是必要的,这些初始B细胞能够在针对病原体的免疫反应和疫苗接种过程中对广泛的抗原作出反应。兔子多年来一直被用于产生高亲和力的单克隆和多克隆抗体。兔子体内产生的特异性抗体极大地推动了科学发现,但兔子B细胞发育的独特特性一直未得到充分认识。与人类和小鼠不同,人类和小鼠的B淋巴细胞生成在中年到老年时会下降,而兔子的B淋巴细胞生成在生命早期,即2至4个月大时就会停止。本综述重点关注兔子B细胞发育的早期丧失以及骨髓微环境对这一过程的贡献。我们还提出了该领域未来研究方向,并讨论了如何将兔子用作模型来理解人类生命后期发生的B淋巴细胞生成下降。此类研究对于开发旨在预防和/或逆转老年人B淋巴细胞生成下降的治疗方法,以及增强感染或疫苗接种后的免疫力和抗体反应将具有重要意义。