B cell TLRs and induction of immunoglobulin class-switch DNA recombination

Egest J. Pone, Zhenming Xu, Clayton A. White, Hong Zan, Paolo Casali

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Toll-like receptors (TLRs) are a family of conserved pattern recognition receptors (PRRs). Engagement of B cell TLRs by microbe-associated molecular patterns (MAMPs) induces T-independent (TI) antibody responses and plays an important role in the early stages of T-dependent (TD) antibody responses before specific T cell help becomes available. The role of B cell TLRs in the antibody response is magnified by the synergy of B cell receptor (BCR) crosslinking and TLR engagement in inducing immunoglobulin (Ig) class switch DNA recombination (CSR), which crucially diversifies the antibody biological effector functions. Dual BCR/TLR engagement induces CSR to all Ig isotypes, as directed by cytokines, while TLR engagement alone induces marginal CSR. Integration of BCR and TLR signaling results in activation of the canonical and non-canonical NF-κB pathways, induction of activation-induced cytidine deaminase (AID) and germline transcription of IgH switch (S) regions. A critical role of B cell TLRs in CSR and the antibody response is emphasized by the emergence of several TLR ligands as integral components of vaccines that greatly boost humoral immunity in a B cell-intrinsic fashion.

Original languageEnglish (US)
Pages (from-to)2594-2615
Number of pages22
JournalFrontiers in Bioscience
Volume17
Issue number7
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Keywords

  • AID
  • Activation-induced cytidine deaminase
  • Adaptive immunity
  • Adjuvant
  • Antibody
  • Antigen
  • Antigen-Specific
  • Autoimmunity
  • B cell
  • B cell receptor
  • BCR
  • CD41
  • CSR
  • Class switch DNA recombination
  • CpG
  • Cytokine
  • Endosome
  • GC
  • Germinal center
  • Germline transcription
  • Immune Deficiency
  • Immunoglobulin Ig
  • Innate immunity
  • Lipid A
  • Lipopolysaccharides LPS
  • MAMPs
  • Microbe-associated molecular patterns
  • NF-κB
  • Natural antibodies
  • Polyclonal
  • SHM
  • Secondary lymphoid organs
  • Signaling
  • Somatic hypermutation
  • T-dependent responses
  • T-independent antibody responses
  • TLR
  • Toll-like receptor
  • Vaccine

ASJC Scopus subject areas

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

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