CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade

Joseph M. Tuscano, Agostino Riva, Salvador N. Toscano, Thomas F. Tedder, John H. Kehrl

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

CD22 is a B-cell-specific adhesion molecule that modulates BCR-mediated signal transduction. Ligation of human CD22 with monoclonal antibodies (MoAbs) that block the ligand binding site triggers rapid tyrosine phosphorylation of CD22 and primary B-cell proliferation. Because extracellular signal-regulated kinases (ERKs) couple upstream signaling pathways to gene activation and are activated by B-cell antigen receptor (BCR) signaling, we examined whether CD22 ligation also activated ERKs and/or modified BCR-induced ERK activation. Ligation of CD22 on either primary B cells or B-cell lines failed to significantly activate the mitogen activated protein kinase (MAPK) ERK-2, but did activate the stress-activated protein kinases (SAPKs; c-jun NH2-terminal kinases or JNKs). In contrast, BCR ligation resulted in ERK-2 activation without significant SAPK activation. Concurrent ligation of CD22 and BCR enhanced BCR-mediated ERK-2 activation without appreciably modulating CD22-induced SAPK activation. Consistent with its induction of SAPK activity, there was a marked increase in nuclear extracts of activator protein-1 (AP-1) and c-jun levels within 2 hours of exposure of primary B cells to the CD22 MoAb. Despite their differences in ERK activation, both CD22 and BCR ligation triggered several Burkitt lymphoma cell lines to undergo apoptosis, and the 2 stimuli together induced greater cell death than either signal alone. The pro-apoptotic effects were CD22- blocking MoAb-specific and dose-dependent. Examination of expression levels of Bcl-2 protoncogene family members (Bcl-2, Bcl-X(L), Mcl-1, and Bax) showed a downregulation of Bcl-X(L) and Mcl-1 after CD22 ligation. This study provides a plausible mechanism to explain how CD22 and BCR signaling can costimulate B-cell proliferation and induce apoptosis in Burkitt lymphoma cell lines.

Original languageEnglish (US)
Pages (from-to)1382-1392
Number of pages11
JournalBlood
Volume94
Issue number4
StatePublished - Aug 15 1999

Fingerprint

B-Cell Antigen Receptors
Ligation
Chemical activation
B-Lymphocytes
Extracellular Signal-Regulated MAP Kinases
Cells
Mitogen-Activated Protein Kinase 1
Burkitt Lymphoma
Cell proliferation
Cell Line
Cell Proliferation
Apoptosis
Signal transduction
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Cell Adhesion Molecules
Cell death
Heat-Shock Proteins
Mitogen-Activated Protein Kinases

ASJC Scopus subject areas

  • Hematology

Cite this

CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. / Tuscano, Joseph M.; Riva, Agostino; Toscano, Salvador N.; Tedder, Thomas F.; Kehrl, John H.

In: Blood, Vol. 94, No. 4, 15.08.1999, p. 1382-1392.

Research output: Contribution to journalArticle

Tuscano, JM, Riva, A, Toscano, SN, Tedder, TF & Kehrl, JH 1999, 'CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade', Blood, vol. 94, no. 4, pp. 1382-1392.
Tuscano, Joseph M. ; Riva, Agostino ; Toscano, Salvador N. ; Tedder, Thomas F. ; Kehrl, John H. / CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. In: Blood. 1999 ; Vol. 94, No. 4. pp. 1382-1392.
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