Cell Reports
Volume 25, Issue 12, 18 December 2018, Pages 3342-3355.e5
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Article
Autoreactive, Low-Affinity T Cells Preferentially Drive Differentiation of Short-Lived Memory B Cells at the Expense of Germinal Center Maintenance

https://doi.org/10.1016/j.celrep.2018.11.070Get rights and content
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Highlights

  • B cell fate choices differ in response to model foreign and self-antigen

  • TCR affinity for antigen influences memory B cell differentiation

  • The GC response to MOG antigen is short lived

  • Formation of B cell memory to MOG antigen is defective

Summary

B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte glycoprotein (MOG) and compare the response with a standard model foreign antigen. Both antigens generate productive primary responses, as evidenced by GC development, circulating antigen-specific antibodies, and differentiation of memory B cells. However, in the MOG response, the status of the cognate T cell partner drives preferential B cell differentiation to a memory phenotype at the expense of GC maintenance, resulting in a truncated GC. Reduced plasma cell differentiation is largely independent of T cell influence. Interestingly, memory-phenotype B cells formed in the MOG GC are not long lived, resulting in a failure of the B cell response to secondary challenge.

Keywords

B cell
T follicular helper cell
autoimmunity
germinal center
MOG
memory B cell
plasma cell
multiple sclerosis

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