IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice

Jin Huk Choi, Kuan Wen Wang, Duan-Wu Zhang Ph.D., Xiaowei Zhan, Tao Wang, Chun Hui Bu, Cassie L. Behrendt, Ming Zeng, Ying Wang, Takuma Misawa, Xiaohong Li, Miao Tang, Xiaoming Zhan, Lindsay Scott, Sara Hildebrand, Anne R. Murray, Eva Marie Y Moresco, Lora V Hooper, Bruce A Beutler

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. IgD overproduction was dependent on activation-induced cytidine deaminase, hematopoietic MyD88 expression, and an intact microbiome, against which circulating IgD, but not IgM, was reactive. IgD CSR occurred via both alternative nonhomologous end-joining and homologous recombination pathways. Microbiota-dependent IgD CSR also was detected in nasal-associated lymphoid tissue of WT mice. These results identify a pathway, present in WT mice and hyperactivated in 53BP1-deficient mice, by which microbiota signal via Toll-like receptors to elicit IgD CSR.

Original languageEnglish (US)
Pages (from-to)E1196-E1204
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number7
DOIs
StatePublished - Feb 14 2017

Keywords

  • 53BP1
  • Class-switch recombination
  • IgD
  • Microbiota
  • Toll-like receptor

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice'. Together they form a unique fingerprint.

  • Cite this

    Choi, J. H., Wang, K. W., Zhang Ph.D., D-W., Zhan, X., Wang, T., Bu, C. H., Behrendt, C. L., Zeng, M., Wang, Y., Misawa, T., Li, X., Tang, M., Zhan, X., Scott, L., Hildebrand, S., Murray, A. R., Moresco, E. M. Y., Hooper, L. V., & Beutler, B. A. (2017). IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice. Proceedings of the National Academy of Sciences of the United States of America, 114(7), E1196-E1204. https://doi.org/10.1073/pnas.1621258114