Jchain-Diphtheria Toxin Receptor Mice Allow for Diphtheria Toxin-Mediated Depletion of Antibody-Secreting Cells and Analysis of Differentiation Kinetics

Abstract

Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs play key roles in humoral immunity, including responses to pathogens, vaccination, and homeostatic clearance of cell debris. Therefore, understanding basic tenents of ASC biology such as their differentiation kinetics following B cell stimulation is of importance. We developed a mouse model which expresses simian heparin-binding EGF-like growth factor (HBEGF) [diphtheria toxin receptor (DTR)] under the control of the endogenous Jchain locus (J-DTR). ASCs from J-DTR 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 J-DTR mice to track ASC reconstitution following depletion in the spleen, bone marrow and thymus which represent sites of ASC generation and/or retention. 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.