Early Emergence of Adaptive Mechanisms Sustaining Ig Production: Application to Antibody Therapy.

Autor:	Lemarié M; Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, Rennes, France., Chatonnet F; Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, Rennes, France.; Laboratoire d'Hématologie, Pôle de Biologie, Centre Hospitalier Universitaire, Rennes, France., Caron G; Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, Rennes, France.; Laboratoire d'Hématologie, Pôle de Biologie, Centre Hospitalier Universitaire, Rennes, France., Fest T; Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, Rennes, France.; Laboratoire d'Hématologie, Pôle de Biologie, Centre Hospitalier Universitaire, Rennes, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Apr 29; Vol. 12, pp. 671998. Date of Electronic Publication: 2021 Apr 29 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.671998
Abstrakt:	Antibody therapy, where artificially-produced immunoglobulins (Ig) are used to treat pathological conditions such as auto-immune diseases and cancers, is a very innovative and competitive field. Although substantial efforts have been made in recent years to obtain specific and efficient antibodies, there is still room for improvement especially when considering a precise tissular targeting or increasing antigen affinity. A better understanding of the cellular and molecular steps of terminal B cell differentiation, in which an antigen-activated B cell becomes an antibody secreting cell, may improve antibody therapy. In this review, we use our recently published data about human B cell differentiation, to show that the mechanisms necessary to adapt a metamorphosing B cell to its new secretory function appear quite early in the differentiation process i.e., at the pre-plasmablast stage. After characterizing the molecular pathways appearing at this stage, we will focus on recent findings about two main processes involved in antibody production: unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. We'll show that many genes coding for factors involved in UPR and ER stress are induced at the pre-plasmablast stage, sustaining our hypothesis. Finally, we propose to use this recently acquired knowledge to improve productivity of industrialized therapeutic antibodies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Lemarié, Chatonnet, Caron and Fest.)
Databáze:	MEDLINE
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