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Related Experiment Videos

Extracellular calcium sensing promotes human B-cell activation and function.

Caitlin M Hammond1, Dionne White, Jelena Tomic

  • 1Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Blood
|August 29, 2007
PubMed
Summary
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Human B cells possess a novel calcium receptor that triggers internal calcium release and activates key signaling pathways. This sensor enhances B cell responses to immune stimuli, preparing them for action.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Calcium ions act as crucial second messengers in numerous B cell signaling pathways.
  • The specific role of calcium as a direct receptor ligand in B cells remains incompletely understood.
  • Extracellular calcium's influence on B cell function warrants further investigation.

Purpose of the Study:

  • To characterize the function and identity of a potential calcium receptor on human B cells.
  • To elucidate the signaling pathways activated by extracellular calcium in B cells.
  • To determine how extracellular calcium sensing impacts B cell responsiveness to other immune triggers.

Main Methods:

  • Investigated calcium-induced responses in human B cells.
  • Utilized enzymatic (trypsin) and chemical inhibitors (kinase, phospholipase Cgamma) to probe receptor mediation.

Related Experiment Videos

  • Assessed B cell signaling pathway activation (e.g., PI3K/AKT, ERK, p38 MAPK, PKC, CaMKII, NF-kB) via Western blotting and gene expression analysis.
  • Confirmed the absence of the conventional calcium-sensing receptor (CaSR) and its inhibitors' ineffectiveness.

    • Main Results:

    • Extracellular calcium triggered rapid release of internal calcium stores in B cells.
    • This calcium-induced response was mediated by a trypsin-sensitive cell surface protein, distinct from CaSR.
    • Activation of multiple signaling cascades including PI3K/AKT, ERK, p38 MAPK, PKC, CaMKII, and NF-kB was observed.
    • Extracellular calcium sensing led to CD83 gene transcription and enhanced B cell responses to TLR, BCR, and cytokine receptor agonists.

    Conclusions:

    • Human B cells possess a novel extracellular calcium sensor that modulates immune signaling.
    • This sensor activates critical intracellular pathways and primes B cells for enhanced responses to immune stimuli.
    • The findings reveal a mechanism by which B cells integrate calcium fluctuations into their immune surveillance and activation processes.