Activation-induced deaminase contributes to the antibody-independent role of B cells in the development of autoimmunity.

Autoimmunity
Chuancang JiangMarilyn Diaz

Abstract

B cells contribute to autoimmunity both as secretors of pathogenic antibodies and through the activation of autoreactive T cells. B cells and antibodies acquire higher affinity to self-antigen through a process known as immunoglobulin hypermutation or SHM. The contribution of SHM to pathogenic antibody development in lupus has been established in various autoimmune mouse models and by examining antibodies from patients. However, its role in the antibody-independent contribution of B cells to autoimmunity has not been examined. Herein, we generate lupus-prone MRL/lpr mice with a limited IgM-only B cell repertoire, no secreted antibodies and no SHM. This enabled us to isolate the role of somatic hypermutation in B cell-mediated autoimmunity. We found that SHM-deficiency correlated with a reduction in autoreactive B cells, a decrease in T cell activation and a decrease in kidney lymphocytic infiltration. These data establish AID as an important contributor to the antibody-independent role of B cells in autoimmunity.

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Citations

Aug 27, 2013·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Aug 29, 2014·Biomedical Journal·Ritu KumarTodd Evans
Dec 12, 2012·Autoimmunity·Marilyn Diaz
Mar 3, 2017·Gastroenterology Research and Practice·Raffaella LiccardoFrancesca Duraturo
Nov 28, 2012·Autoimmunity·Elisabetta IncorvaiaKerstin-Maike Schmitz

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