Antigen presentation by B cells enables epitope spreading across an MHC barrier

Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Ewa Terczyńska-Dyla, Kristian Savstrup Kastberg, Emily Yang, Alysa Nicole Rallistan, Quinton Raymond Markett, Gudrun Winther, Sofie Fonager, Lasse F. Voss, Mathias K. Pedersen, Nina van Campen, Alexey Ferapontov, Lisbeth Jensen, Jinrong Huang, John D. Nieland, Cees E. van der Poel, Johan Palmfeldt, Michael C. Carroll, Paul J. UtzYonglun Luo, Lin Lin, Søren E. Degn*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review


Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

TidsskriftNature Communications
Antal sider21
StatusUdgivet - dec. 2023


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