Daley-Bauer L P, Purdy S R, Smith M C, Gagliardo L F, Davis W C, Appleton J A
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Clin Vaccine Immunol. 2010 Dec;17(12):2007-15. doi: 10.1128/CVI.00287-10. Epub 2010 Oct 6.
In addition to conventional immunoglobulins, camelids produce antibodies that do not incorporate light chains into their structures. These so-called heavy-chain (HC) antibodies have incited great interest in the biomedical community, as they have considerable potential for biotechnological and therapeutic application. Recently, we have begun to elucidate the immunological functions of HC antibodies, yet little is known about their significance in maternal immunity or about the B lymphocytes that produce them. This study describes the application of isotype-specific reagents toward physiological assessments of camelid IgGs and the B cells that produce them. We document the specificities of monoclonal antibodies that distinguish two conventional IgG1 isotypes and two HC IgG3 variants produced by alpacas. Next, we report that the relative concentrations of five isotypes are similar in serum, milk, and colostrum; however, following passive transfer, the concentrations of HC IgG2 and IgG3 declined more rapidly than the concentration of conventional IgG1 in the sera of neonates. Finally, we assessed the distribution of B cells of distinct isotypes within lymphoid tissues during fetal and adult life. We detected IgG1, IgG2, and IgG3 in lymphocytes located in lymph node follicles, suggesting that HC B cells affinity mature and/or class switch. One IgG3 isotype was present in B cells located in ileal Peyer's patches, and one conventional IgG1 isotype was detected in splenic marginal zone B cells. Our findings contribute to the growing body of knowledge pertaining to HC antibodies and are compatible with functional specialization among conventional and HC IgGs in the alpaca.
除了传统免疫球蛋白外,骆驼科动物还产生结构中不包含轻链的抗体。这些所谓的重链(HC)抗体引起了生物医学界的极大兴趣,因为它们在生物技术和治疗应用方面具有相当大的潜力。最近,我们开始阐明HC抗体的免疫功能,但对其在母体免疫中的意义或产生它们的B淋巴细胞了解甚少。本研究描述了同型特异性试剂在骆驼科动物IgG及其产生的B细胞生理评估中的应用。我们记录了区分羊驼产生的两种传统IgG1同型和两种HC IgG3变体的单克隆抗体的特异性。接下来,我们报告血清、乳汁和初乳中五种同型的相对浓度相似;然而,被动转移后,新生儿血清中HC IgG2和IgG3的浓度下降速度比传统IgG1更快。最后,我们评估了不同同型B细胞在胎儿期和成年期淋巴组织中的分布。我们在位于淋巴结滤泡的淋巴细胞中检测到IgG1、IgG2和IgG3,这表明HC B细胞发生了亲和力成熟和/或类别转换。一种IgG3同型存在于位于回肠派尔集合淋巴结的B细胞中,一种传统IgG1同型在脾边缘区B细胞中被检测到。我们的研究结果有助于增加与HC抗体相关的知识体系,并与羊驼中传统IgG和HC IgG之间的功能特化相一致。