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

Francesca Rampoldi; Elisa Donato; Leon Ullrich; Malte Deseke; Anika Janssen; Abdi Demera; Inga Sandrock; Anja Bubke; Anna-Lena Juergens; Maxine Swallow; Tim Sparwasser; Christine Falk; Likai Tan; Andreas Trumpp; Immo Prinz

doi:10.1016/j.celrep.2022.110854

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.

Authors

Affiliations

¹ Institute of Immunology, Hannover Medical School, Hannover 30625, Germany; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany.
² Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg 69120, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH), Heidelberg 69120, Germany.
³ Institute of Immunology, Hannover Medical School, Hannover 30625, Germany.
⁴ Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover 30625, Germany.
⁵ Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover 30625, Germany.
⁶ Institute of Transplant Immunology, Hannover Medical School, Hannover 30625, Germany.
⁷ Institute of Immunology, Hannover Medical School, Hannover 30625, Germany; Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany.
⁸ Institute of Immunology, Hannover Medical School, Hannover 30625, Germany; Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany. Electronic address: i.prinz@uke.de.

PMID: 35613579
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