Jchain- DTR Mice Allow for Diphtheria Toxin-Mediated Depletion of Antibody-Secreting Cells and Evaluation of Their Differentiation Kinetics

Jchain-DTR 小鼠允许白喉毒素介导的抗体分泌细胞耗竭并评估其分化动力学

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作者:KimAnh T Pioli, Matthew Ritchie, Hira Haq, Peter D Pioli

Abstract

Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs are key mediators of humoral immunity whether it be in the context of pathogen exposure, vaccination or even homeostatic clearance of cellular debris. Therefore, understanding basic tenants of ASC biology such as their differentiation kinetics following B cell stimulation is of importance. Towards that aim, we developed a mouse model which expresses simian HBEGF (a.k.a., diphtheria toxin receptor (DTR)) under the control of the endogenous Jchain locus (or J-DTR). ASCs from these mice expressed high levels of cell surface DTR and were acutely depleted following diphtheria toxin treatment. Furthermore, proof-of-principle experiments demonstrated the ability to use these mice to track ASC reconstitution following depletion in 3 distinct organs. Overall, J-DTR mice provide a new and highly effective genetic tool allowing for the study of ASC biology in a wide range of potential applications.

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