B cell antigen receptor-evoked calcium influx is enhanced in CD22-deficient B cell lines

M J Nadler1, P A McLean, B G Neel

  • 1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Insights

CD22 acts as a negative regulator in B cell signaling. Loss of CD22 increases B cell receptor responsiveness and calcium influx, demonstrating its crucial role in immune cell function.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • CD22 is a B cell membrane glycoprotein involved in immune receptor signaling.
  • Two allelic forms, CD22.1 and CD22.2, exist in mice.
  • Previous research suggested both positive and negative roles for CD22.

Purpose of the Study:

  • To investigate the specific role of CD22 in B cell receptor signal transduction.
  • To elucidate the function of CD22 independent of its developmental role.
  • To understand how CD22 influences cellular responses upon antigen receptor engagement.

Main Methods:

  • Utilized WEHI-231 cell variants with reduced CD22 expression.
  • Examined B cell receptor signaling pathways, including tyrosyl phosphorylation and calcium flux.
  • Assessed the association between CD22 and the protein-tyrosine phosphatase SHP-1.
  • Reconstituted CD22 expression to confirm findings.

Main Results:

  • B cell variants with reduced CD22 showed hyper-responsiveness to antigen receptor stimulation.
  • Increased tyrosyl phosphorylation of cellular proteins and enhanced calcium influx were observed.
  • The association between SHP-1 and CD22 was reduced in CD22-deficient cells.
  • Re-expression of CD22 reversed these signaling alterations.

Conclusions:

  • CD22 functions as a cell-autonomous negative regulator of B cell antigen receptor signaling.
  • CD22 appears to regulate calcium entry, potentially downstream of or independent of intracellular calcium release.
  • These findings clarify the inhibitory role of CD22 in B cell activation.

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