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

Highlight of 2023: Thymic B cells—important players in the establishment of T‐cell tolerance

“…To test the role of thymic B-cell CSR on T-cell development, our group investigated thymic B-cell phenotypes in a panel of genetically divergent mouse strains. 13 Interestingly, the presence of isotype-switched thymic B cells was observed in all tested strains (4-40% of total thymic B cells). Strikingly, the NOD mouse, a widely used model of type 1 diabetes, 14 presented with the lowest proportion of isotype-switched thymic B cells.…”

“…While class switch recombination (CSR) had been previously described in thymic B cells in great detail, 5,12 its impact on thymic B‐cell function had not been directly investigated. To test the role of thymic B‐cell CSR on T‐cell development, our group investigated thymic B‐cell phenotypes in a panel of genetically divergent mouse strains 13 . Interestingly, the presence of isotype‐switched thymic B cells was observed in all tested strains (4–40% of total thymic B cells).…”

Thymus antibody-secreting cells: once forgotten but not lost

“…While the full Ab repertoire of these cells is unknown, autoreactive B cells have been identified in both the human and mouse THY even under healthy conditions ( 45 , 46 ). Upon first glance, this seems inherently detrimental; however, multiple studies based in mice have revealed the ability of autoreactive THY B cells to regulate negative selection of CD4 single positive T cells ( 45 , 47 – 49 ) and to augment the production of regulatory T cells ( 50 , 51 ). Thus, the presence of autoreactive THY B cells seems to be a necessary component to systemic immune tolerance.…”

“…Thus, the presence of autoreactive THY B cells seems to be a necessary component to systemic immune tolerance. During this tolerogenic process, THY B cells undergo AID dependent class switching ( 45 , 47 ) indicative of a productive immune response. Data indicate this requires cognate B cell-T cell interactions as class switching was abrogated upon deletion of major histocompatibility complex (MHC) II and CD40 as well as in T cell receptor (TCR) transgenic mice whose CD4 T cells were specific for ovalbumin ( 45 ).…”

“…These B cells then directly interact with developing CD4 T cells via CD154:CD40 inducing Aire in THY B cells and the ability to express tissue-restricted antigens ( 57 , 67 ) that are then processed and presented to CD4 T cells via MHC II. These events ultimately lead to the negative selection, or apoptosis, of cognate autoreactive T cells ( 45 , 47 , 48 ). In this scenario, THY B cells do not expand nor produce significant amounts of THY ASCs as supported by the inability of in vivo αCD40 treatment to increase these THY populations ( 37 ).…”