B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota

Lieselotte Sm Kreuk, Meghan A. Koch, Leianna C. Slayden, Nicholas A. Lind, Sophia Chu, Hannah P. Savage, Aaron B. Kantor, Nicole Baumgarth, Gregory M. Barton

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of 'natural' IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Aug 21 2019

Fingerprint

Toll-Like Receptors
Microbiota
B-Lymphocytes
Cells
Antibodies
Phosphatidylcholines
Tissue homeostasis
Antigens
Autoantigens
Nucleic Acids
Antibody Formation
Immunoglobulin M
Immunoglobulins
Homeostasis
Chemical activation
Infection
Serum
immunoglobulin B

Keywords

  • antibodies
  • B cells
  • immunology
  • inflammation
  • microbiota
  • mouse
  • Toll-like receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Kreuk, L. S., Koch, M. A., Slayden, L. C., Lind, N. A., Chu, S., Savage, H. P., ... Barton, G. M. (2019). B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota. eLife, 8. https://doi.org/10.7554/eLife.47015

B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota. / Kreuk, Lieselotte Sm; Koch, Meghan A.; Slayden, Leianna C.; Lind, Nicholas A.; Chu, Sophia; Savage, Hannah P.; Kantor, Aaron B.; Baumgarth, Nicole; Barton, Gregory M.

In: eLife, Vol. 8, 21.08.2019.

Research output: Contribution to journalArticle

Kreuk, Lieselotte Sm ; Koch, Meghan A. ; Slayden, Leianna C. ; Lind, Nicholas A. ; Chu, Sophia ; Savage, Hannah P. ; Kantor, Aaron B. ; Baumgarth, Nicole ; Barton, Gregory M. / B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota. In: eLife. 2019 ; Vol. 8.
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