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Article Dans Une Revue Frontiers in Immunology Année : 2021

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

Résumé

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.

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Immunothérapie
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hal-03260854 , version 1 (15-06-2021)

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Maud Lemarié, Fabrice Chatonnet, Gersende Caron, Thierry Fest. Early Emergence of Adaptive Mechanisms Sustaining Ig Production: Application to Antibody Therapy. Frontiers in Immunology, 2021, 12, pp.671998. ⟨10.3389/fimmu.2021.671998⟩. ⟨hal-03260854⟩
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