IMR Press / FBL / Volume 17 / Issue 7 / DOI: 10.2741/4073

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

B cell TLRs and induction of immunoglobulin class-switch DNA recombination
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1 Institute for Immunology, School of Medicine, University of California, Irvine, CA 92697-4120, U.S.A.
Front. Biosci. (Landmark Ed) 2012, 17(7), 2594–2615;
Published: 1 June 2012

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.

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