Efficient adoptive transfer of autologous modified B cells: a new humanized platform mouse model for testing B cells reprogramming therapies

Here, we report a novel experimental setup to perform adoptive transfer of gene-edited B cells using humanized immune system mice by infusing autologous HIS mouse-derived human B cells educated in a murine context and thus rendered tolerant to the host. The present approach presents two advantages over the conventional humanized PBMC mouse models: (i) it circumvents the risk of xenogeneic graft-versus-host reaction and (ii) it mimics more closely human immune responses, thus favoring clinical translation. We show that the frequencies and numbers of transduced B cells in recipient's spleens one week post-transfer are within the range of the size of the pre-immune B cell population specific for a given protein antigen in the mouse. They are also compatible with the B cell numbers required to elicit a sizeable immune response upon immunization. Altogether, our findings pave the way for future studies aiming at assessing therapeutic interventions involving B cell reprogramming for instance by an antibody transgene in a humanized hematopoietic setting.

Automated summary

This study introduces a novel experimental approach for adoptive transfer of gene-edited B cells in humanized immune system mice, bypassing the risk of xenogeneic graft-versus-host reaction and closely mimicking human immune responses for potential clinical applications. Results show that the transduced B cells post-transfer in recipient's spleens are comparable to pre-immune B cell populations specific for certain protein antigens in mice, suggesting the potential for eliciting significant immune responses upon immunization.