Lachkar, S. | bioRxiv Science

bioRxiv2025

Humanized mice enable in vivo evaluation of engineered plasma cell biology and therapeutic function

Engineered plasma cells (ePCs) offer a durable strategy for in vivo delivery of therapeutic antibodies, but standard immunodeficient mouse models lack human immune factors critical for plasma cell survival and function. We utilized a humanized mouse model in which NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were engrafted with human CD34+ stem cells as recipients for infusions with autologous ePCs. In this setting, ePCs localized to plasma cell niches and stably secreted antibodies for over three months. To improve the selection of antibodies for secretion, we developed a B cell receptor surface display screen that identified candidate antibody sequences with high secretion potential. An anti-SARS-CoV-2 antibody (clone 297) selected by this method showed robust secretion both in vitro and vivo, and serum from ePC-engrafted mice potently neutralized SARS-CoV-2 pseudovirus. Together, these findings establish a physiologically relevant model for testing human ePCs, and offer a generalizable strategy for optimizing antibody selection to support long-term therapeutic delivery.

molecular biology↗

bioRxiv2021

Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors

Microtubule dynamics is regulated by various cellular proteins and perturbed by small molecule compounds. To what extent the mechanism of the former resembles that of the latter is an open question. We report here structures of tubulin bound to the PN2-3 domain of CPAP, a protein controlling the length of the centrioles. We show that an -helix of the PN2-3 N-terminal region binds and caps the longitudinal surface of the tubulin {beta} subunit. Moreover, a PN2-3 N-terminal stretch lies in a {beta}-tubulin site also targeted by fungal and bacterial peptide-like inhibitors of the vinca domain, sharing a very similar binding mode with these compounds. Therefore, our results identify several characteristic features of cellular partners that bind to this site and highlight a structural convergence of CPAP with small molecule inhibitors of microtubule assembly.

biochemistry↗