CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase

Chandrasekar Venkataraman, Pei Jung Lu, Anne Mette Buhl, Ching Shih Chen, John C. Cambier, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Occupancy of the B cell glycoprotein, CD72 results in syk-independent activation of phospholipase-C γ and calcium mobilization. The cytoplasmic tail of CD72 does not contain an immunoreceptor tyrosine-based activation motif to directly transduce signals into the B lymphocyte. Hence, we investigated whether other coreceptors such as CD19 and its associated phosphatidylinositol 3-kinase (Pl 3-K) were involved in CD72 signaling. Two specific inhibitors of Pl 3-K inhibited CD72-stimulated B cell proliferation in a dose-dependent manner. Activation of B lymphocytes via CD72 resulted in recruitment and activation of Pl 3-K, which was mediated by CD19. Accordingly, CD72 ligation induced CD19 tyrosine phosphorylation. Thus, lipid products generated as a result of Pl 3-K activation may have an important function in CD72-mediated B lymphocyte activation. The kinetics of CD19 tyrosine phosphorylation induced by CD72 ligation were strikingly different from those seen following B cell antigen receptor (BCR) stimulation. A transient increase in the tyrosine phosphorylation of the complement receptors, CD21 and CD35 was observed in BCR- but not CD72-stimulated cells. Co-cross-linking of CD72 and CD19 failed to induce syk tyrosine phosphorylation suggesting that even under these conditions, CD72 signaling was independent of syk activation. A transient and stimulation-dependent physical association between CD19 and CD72 was observed in CD72-ligated cells. These observations suggest a mechanism by which CD72 can recruit CD19 and influence activation of CD19-associated Pl 3-K, which appears to be critical for CD72-mediated B cell activation.

Original languageEnglish
Pages (from-to)3003-3016
Number of pages14
JournalEuropean Journal of Immunology
Volume28
Issue number10
DOIs
Publication statusPublished - 1998 Oct

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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