T cell help shapes B cell tolerance

Sci Immunol. 2024 Feb 16;9(92):eadj7029. doi: 10.1126/sciimmunol.adj7029. Epub 2024 Feb 16.

Abstract

T cell help is a crucial component of the normal humoral immune response, yet whether it promotes or restrains autoreactive B cell responses remains unclear. Here, we observe that autoreactive germinal centers require T cell help for their formation and persistence. Using retrogenic chimeras transduced with candidate TCRs, we demonstrate that a follicular T cell repertoire restricted to a single autoreactive TCR, but not a foreign antigen-specific TCR, is sufficient to initiate autoreactive germinal centers. Follicular T cell specificity influences the breadth of epitope spreading by regulating wild-type B cell entry into autoreactive germinal centers. These results demonstrate that TCR-dependent T cell help can promote loss of B cell tolerance and that epitope spreading is determined by TCR specificity.

MeSH terms

  • Antigens
  • B-Lymphocytes*
  • Epitopes
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes*

Substances

  • Receptors, Antigen, T-Cell
  • Antigens
  • Epitopes