IFN-alpha induces homotypic adhesion and Leu-13 expression in human B lymphoid cells.
IFN-alpha influences the recirculation and growth of normal and malignant B lymphocytes, although the mechanisms involved are not currently known. Lymphocyte recirculation is fundamentally dependent on cell-to-cell interactions that are mediated by cell surface adhesion molecules. In this report, we examined the relationship between the effect of IFN-alpha on cell-to-cell adhesion processes and induction of the Leu-13 cell surface protein in established human Daudi B lymphoid cell lines that are either sensitive or resistant to the antiproliferative activity of IFN-alpha. IFN-alpha directly triggered homotypic adhesion of IFN-sensitive Daudi B cells in a time- and dose-dependent manner. In contrast, IFN-alpha had no effect on the cell-to-cell adhesion of IFN-resistant Daudi B cells. The capacity of IFN-alpha to trigger homotypic aggregation correlated directly with the level of induction of the cell surface protein Leu-13 and could be potentiated by anti-Leu-13 mAb. Other cytokines also known to influence the proliferation, differentiation, or recirculation of B lymphocytes such as IFN-gamma, IL-2, IL-4, IL-6, TNF-alpha, and low molecular weight B cell growth factor did not induce either Leu-13 expression or homotypic aggregation of Daudi B cells. The adhesion pathway triggered by the IFN-inducible protein Leu-13 required metabolic energy and an intact cytoskeleton but was not dependent on: 1) new protein synthesis; 2) protein kinase C, protein kinase A, or tyrosine kinase activities; or 3) the function of known adhesion molecules including LFA-1, ICAM-1, CD44, or VLA-4. Taken together, these studies demonstrate a fundamental role for IFN-alpha and the IFN-inducible protein Leu-13 in regulating a novel homotypic adhesion pathway in B lymphocytes, and provide insight into the possible mechanisms by which IFN-alpha regulates biologic processes including recirculation.
Evans
S S
SS
Department of Molecular Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Collea
R P
RP
Leasure
J A
JA
Lee
D B
DB
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016898:Interferon-alpha; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; C062010:leu-13 antigen; D013755:Tetradecanoylphorbol Acetate