Constitutive endocytosis and degradation of CD22 by human B cells.
The CD22 B lymphocyte-surface Ag is an important component of the B cell-surface IgM (sIgM)/B cell receptor complex and has been shown to regulate B cell activation. In addition, this molecule has been shown to be an effective target for immunotherapy of B cell malignancies using immunotoxins and radioimmunoconjugates. In this report we describe the internalization and metabolic degradation of this molecule under constitutive conditions and after stimulation of B cells with phorbol dibutyrate or mAbs binding to sIgM, CD19, and CD22. Flow cytometry, "neuraminidase protection," and "neuraminidase shift" assays demonstrated that CD22 is internalized constitutively by unstimulated B cell lines and subsequently degraded in an acidic intracellular compartment (presumably lysosomes) without detectable recycling of the molecule back to the cell surface. Ligation of CD22 with anti-CD22 mAbs markedly increased CD22 internalization but did not affect the rate of intracellular degradation of CD22, suggesting that anti-CD22 mAbs perturb the intracellular trafficking of CD22. In contrast, CD22 internalization and degradation was unaffected by stimulation of B cell lines with phorbol dibutyrate or ligation of other components of the B cell receptor complex (e.g. CD19, sIgM) with mAbs. These patterns of internalization and degradation under constitutive and stimulated conditions contrast with those reported for other lymphoid differentiation Ags (e.g., the TCR, CD3, CD4, and the transferrin receptor), and may help explain the utility of this molecule as a target for immunoconjugate therapy.
Shan
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Department of Medicine, University of Washington, Seattle 98195, USA.
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D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001345:Autoradiography; D001402:B-Lymphocytes / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D004705:Endocytosis / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D037102:Lectins; D018613:Microscopy, Confocal; D009439:Neuraminidase / Q000378:metabolism; D011233:Precipitin Tests; D011863:Radioimmunoassay; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D009439:Neuraminidase