γδ T cells license immature B cells to produce a broad range of polyreactive antibodies

Cell Rep. 2022 May 24;39(8):110854. doi: 10.1016/j.celrep.2022.110854.

Abstract

Immature autoreactive B cells are present in all healthy individuals, but it is unclear which signals are required for their maturation into antibody-producing cells. Inducible depletion of γδ T cells show that direct interaction between γδ T cells and immature B cells in the spleen support an "innate" transition to mature B cells with a broad range of antigen specificities. IL-4 production of γδ T cells and cell-to-cell contact via CD30L support B cell maturation and induce genes of the unfolded protein response and mTORC1 signaling. Eight days after in vivo depletion of γδ T cells, increased numbers of B cells are already stuck in the transitional phase and express increased levels of IgD and CD21. Absence of γδ T cells leads also to reduced levels of serum anti-nuclear autoantibodies, making γδ T cells an attractive target to treat autoimmunity.

Keywords: CP: Immunology; IL-4; autoimmunity; innate help; polyreactive antibodies; transitional B cells; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • B-Lymphocytes
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Precursor Cells, B-Lymphoid* / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta* / metabolism
  • T-Lymphocytes

Substances

  • Antibodies
  • Receptors, Antigen, T-Cell, gamma-delta