Cell reports · 2023
Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Friman Vanda, Quinti Isabella, Davydov Alexey N, Shugay Mikhail, Farroni Chiara, Engström Erik, Pour Akaber Shirin, Barresi Sabina, Mohamed Ahmed, Pulvirenti Federica, Milito Cinzia, Granata Guido, Giorda Ezio, Ahlström Sara, Karlsson Johanna, Marasco Emiliano, Marcellini Valentina, Bocci Chiara, Cascioli Simona, Scarsella Marco, Phad Ganesh, Tilevik Andreas, Tartaglia Marco, Bemark Mats, Chudakov Dmitriy M, Carsetti Rita, Grimsholm Ola
Аннотация
Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.