B cell residency but not T cell-independent IgA switching in the gut requires innate lymphoid cells

Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):e2106754118. doi: 10.1073/pnas.2106754118.

Abstract

Immunoglobulin A (IgA)-producing plasma cells derived from conventional B cells in the gut play an important role in maintaining the homeostasis of gut flora. Both T cell-dependent and T cell-independent IgA class switching occurs in the lymphoid structures in the gut, whose formation depends on lymphoid tissue inducers (LTis), a subset of innate lymphoid cells (ILCs). However, our knowledge on the functions of non-LTi helper-like ILCs, the innate counter parts of CD4 T helper cells, in promoting IgA production is still limited. By cell adoptive transfer and utilizing a unique mouse strain, we demonstrated that the generation of IgA-producing plasma cells from B cells in the gut occurred efficiently in the absence of both T cells and helper-like ILCs and without engaging TGF-β signaling. Nevertheless, B cell recruitment and/or retention in the gut required functional NKp46-CCR6+ LTis. Therefore, while CCR6+ LTis contribute to the accumulation of B cells in the gut through inducing lymphoid structure formation, helper-like ILCs are not essential for the T cell-independent generation of IgA-producing plasma cells.

Keywords: B cell; IgA; T cell; innate lymphoid cell; lymphoid tissue inducer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • GATA3 Transcription Factor / metabolism
  • Gastrointestinal Tract / immunology*
  • Immunity, Innate*
  • Immunoglobulin A / immunology*
  • Immunoglobulin Class Switching* / immunology
  • Integrases / metabolism
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / metabolism

Substances

  • GATA3 Transcription Factor
  • Immunoglobulin A
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse
  • Transforming Growth Factor beta
  • Cre recombinase
  • Integrases