Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity

Félix Lombard-Vadnais; Geneviève Chabot-Roy; Astrid Zahn; Sahily Rodriguez Torres; Javier M Di Noia; Heather J Melichar; Sylvie Lesage

doi:10.1016/j.isci.2022.105852

Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity

iScience. 2022 Dec 21;26(1):105852. doi: 10.1016/j.isci.2022.105852. eCollection 2023 Jan 20.

Authors

Félix Lombard-Vadnais^{1

2}, Geneviève Chabot-Roy¹, Astrid Zahn³, Sahily Rodriguez Torres^{1

4}, Javier M Di Noia^{2

3

5

6}, Heather J Melichar^{1

5}, Sylvie Lesage^{1

4}

Affiliations

¹ Immunologie-oncologie, Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada.
² Department of Microbiology & Immunology, McGill University, Montreal, QC H3A 0G4, Canada.
³ Unité de recherche en biologie moléculaire des cellules B, Institut de recherches cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
⁴ Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC H3T 1J4, Canada.
⁵ Département de médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
⁶ Department of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada.

Abstract

Elimination of self-reactive T cells in the thymus is critical to establish T-cell tolerance. A growing body of evidence suggests a role for thymic B cells in the elimination of self-reactive thymocytes. To specifically address the role of thymic B cells in central tolerance, we investigated the phenotype of thymic B cells in various mouse strains, including non-obese diabetic (NOD) mice, a model of autoimmune diabetes. We noted that isotype switching of NOD thymic B cells is reduced as compared to other, autoimmune-resistant, mouse strains. To determine the impact of B cell isotype switching on thymocyte selection and tolerance, we generated NOD.AID^-/- mice. Diabetes incidence was enhanced in these mice. Moreover, we observed reduced clonal deletion and a resulting increase in self-reactive CD4⁺ T cells in NOD.AID^-/- mice relative to NOD controls. Together, this study reveals that AID expression in thymic B cells contributes to T-cell tolerance.

Keywords: Immunity; Immunology.