Jchain-diphtheria toxin receptor mice: a new tool allowing for the acute depletion of antibody-secreting cells.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B813
Abstract ID: 4426

Presenting Author:
Peter Pioli , Assistant Professor at Univ. of Saskatchewan

Abstract:

Upon activation, mature B cells differentiate into antibody-secreting cells (ASCs) consisting of short-lived plasmablasts and post-mitotic mature plasma cells. These cells play critical roles in host defense through their ability to secrete protective antibodies while also promoting certain T cell responses. Furthermore, ASCs have been shown to regulate processes such as hematopoiesis in an age-dependent manner. As such, the ability to selectively deplete ASCs in a wide variety of experimental settings is extremely valuable in understanding their biological roles. To that end, we generated a mouse model in which the diphtheria toxin receptor (DTR) was knocked into the endogenous Jchain locus without disrupting Jchain expression. This led to high levels of DTR expression by ASCs in multiple tissues. To determine the functionality of this model, we performed studies that acutely depleted ASCs following a single treatment of diphtheria toxin (DT). This resulted in the targeted depletion of ASCs in the bone marrow, spleen and thymus of Jchain-DTR expressing mice. Notably, DT had no effect on ASC populations from wildtype animals. In summary, the Jchain-DTR mouse is a reliable and convenient model to acutely deplete ASCs which has the potential to be applied in numerous research settings.