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Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.

Publication ,  Journal Article
Wheeler, ML; Dong, MB; Brink, R; Zhong, X-P; DeFranco, AL
Published in: Sci Signal
October 15, 2013

Signaling downstream of the B cell antigen receptor (BCR) is tightly regulated to enable cells to gauge the strength and duration of antigen-receptor interactions and to respond appropriately. We investigated whether metabolism of the second messenger diacylglycerol (DAG) by members of the family of DAG kinases (DGKs) played a role in modulating the magnitude of signaling by DAG downstream of the BCR. In the absence of DGKζ, the threshold for BCR signaling, measured as activation of the Ras-extracellular signal-regulated kinase (ERK) pathway, was markedly reduced in mature follicular B cells, which resulted in enhanced responses to antigen in vitro and in vivo. Inhibition of DAG signaling by DGKζ limited the number of antibody-secreting cells that were generated early in response to T cell-independent type 2 antigens, as well as to T cell-dependent antigens. Furthermore, the effect of loss of DGKζ closely resembled the effect of increasing the affinity of the BCR for antigen during the T cell-dependent antibody response. These results suggest that the magnitude of DAG signaling is important for translating the affinity of the BCR for antigen into the amount of antibody produced during the early stages of an immune response.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

October 15, 2013

Volume

6

Issue

297

Start / End Page

ra91

Location

United States

Related Subject Headings

  • bcl-X Protein
  • T-Lymphocytes
  • Receptors, Antigen, B-Cell
  • Plasma Cells
  • Muramidase
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Signaling System
 

Citation

APA
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ICMJE
MLA
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Wheeler, M. L., Dong, M. B., Brink, R., Zhong, X.-P., & DeFranco, A. L. (2013). Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses. Sci Signal, 6(297), ra91. https://doi.org/10.1126/scisignal.2004189
Wheeler, Matthew L., Matthew B. Dong, Robert Brink, Xiao-Ping Zhong, and Anthony L. DeFranco. “Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.Sci Signal 6, no. 297 (October 15, 2013): ra91. https://doi.org/10.1126/scisignal.2004189.
Wheeler ML, Dong MB, Brink R, Zhong X-P, DeFranco AL. Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses. Sci Signal. 2013 Oct 15;6(297):ra91.
Wheeler, Matthew L., et al. “Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.Sci Signal, vol. 6, no. 297, Oct. 2013, p. ra91. Pubmed, doi:10.1126/scisignal.2004189.
Wheeler ML, Dong MB, Brink R, Zhong X-P, DeFranco AL. Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses. Sci Signal. 2013 Oct 15;6(297):ra91.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

October 15, 2013

Volume

6

Issue

297

Start / End Page

ra91

Location

United States

Related Subject Headings

  • bcl-X Protein
  • T-Lymphocytes
  • Receptors, Antigen, B-Cell
  • Plasma Cells
  • Muramidase
  • Mice, Knockout
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Signaling System