Cell Reports (Dec 2018)

Autoreactive, Low-Affinity T Cells Preferentially Drive Differentiation of Short-Lived Memory B Cells at the Expense of Germinal Center Maintenance

  • Rajiv W. Jain,
  • Kate A. Parham,
  • Yodit Tesfagiorgis,
  • Heather C. Craig,
  • Emiliano Romanchik,
  • Steven M. Kerfoot

Journal volume & issue
Vol. 25, no. 12
pp. 3342 – 3355.e5

Abstract

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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. : Jain et al. compare B cell responses to different antigens and find that they preferentially differentiate into short-lived memory-phenotype B cells in response to a myelin autoantigen. This was in part controlled by T cells and influenced by TCR affinity for antigen, demonstrating that antigen characteristics can determine immune outcome. Keywords: B cell, T follicular helper cell, autoimmunity, germinal center, MOG, memory B cell, plasma cell, multiple sclerosis