Borbet Timothy C, Zaldaña Kimberly, Zavitsanou Anastasia-Maria, Hines Marcus J, Bajwa Sofia, Morrison Tate, Boehringer Thomas, Hallisey Victoria M, Cadwell Ken, Koralov Sergei B
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, 10027, USA.
bioRxiv. 2023 Dec 4:2023.12.02.569736. doi: 10.1101/2023.12.02.569736.
Plasma cells (PCs) are essential for humoral immunity, as they are responsible for the production of antibodies and contribute to immunological memory. Despite their importance, differentiating between long-lived and short-lived PCs remains a challenge due to a lack of specific markers to distinguish these populations. Addressing this gap, our study introduces a novel J-chain CreERT2 GFP allele (IgJ) for precise genetic studies of PCs. This model takes advantage of PC-restricted expression of the J-chain gene, enabling temporal and cell-specific tracking of PCs utilizing a tamoxifen-inducible Cre recombinase. Our and validation studies of the inducible Cre allele confirmed the fidelity and utility of this model and demonstrated the model's ability to trace the long-lived PC population following immunization. The IgJ model allowed for detailed analysis of surface marker expression on PCs, revealing insights into PC heterogeneity and characteristics. Our findings not only validate the IgJ mouse as a reliable tool for studying PCs but also facilitate the investigation of PC dynamics and longevity, particularly in the context of humoral immunity and vaccine responses. This model represents a significant advancement for the in-depth study of PCs in health and disease, offering a new avenue for the exploration of PC biology and immunological memory.
浆细胞(PCs)对于体液免疫至关重要,因为它们负责产生抗体并有助于免疫记忆。尽管它们很重要,但由于缺乏区分这些群体的特异性标志物,区分长寿和短命的浆细胞仍然是一项挑战。为了解决这一差距,我们的研究引入了一种新型的J链CreERT2 GFP等位基因(IgJ),用于浆细胞的精确遗传学研究。该模型利用J链基因在浆细胞中的限制性表达,通过他莫昔芬诱导的Cre重组酶实现对浆细胞的时间和细胞特异性追踪。我们对诱导型Cre等位基因的表征和验证研究证实了该模型的保真度和实用性,并证明了该模型在免疫后追踪长寿浆细胞群体的能力。IgJ模型允许对浆细胞表面标志物表达进行详细分析,揭示了浆细胞异质性和特征的见解。我们的研究结果不仅验证了IgJ小鼠是研究浆细胞的可靠工具,还促进了对浆细胞动力学和寿命的研究,特别是在体液免疫和疫苗反应的背景下。该模型代表了在健康和疾病中深入研究浆细胞的重大进展,为探索浆细胞生物学和免疫记忆提供了新途径。