Method of testing the effect of a molecule on B lymphocyte funct

Details Method of testing the effect of a molecule on B lymphocyte funct Method of testing the effect of a molecule on B lymphocyte funct

1989-02-21

1991-01-22

Warden, Robert J.

Chemistry: analytical and immunological testing

Biological cellular material tested

435 29, 435 32, C12Q 102, C12Q 118, G01N 3348

Patent

active

049870840

ABSTRACT:
A method of testing the effect of an agonist or an antagonist to B lymphocyte cell surface protein CD20 on B lymphocyte function which involves determining calcium ion flux across the B lymphocyte membrane, contacting the B lymphocyte with the agonist or antagonist, and determining the change in calcium ion flux across the membrane after exposure of the B lymphocyte to the agonist or antagonist, is described. In preferred embodiments of the method the agonist or antagonist is a ligand that binds CD20 or an antibody to CD20.
In other preferred embodiments, calcium ion flux is more preferably determined in terms of transmembrane current flow and most preferrably determined in terms of the change in cytosloic CA.sup.2+ concentration.

REFERENCES:
Nadler et al., "B Cell Origin of Non-T Cell Acute Lymphoblastic Leukemia A Model for Discrete Stages of Neoplastic and Normal Pre-B Cell Differentiation," J. Clin. Invest. 74: 332-340 (1984).
Tedder et al., "Antibodies Reactive with the B1 Molecule Inhibity Cell Cycle Progression but not Activation of Human B lymphocytes," Eur. J. Immunol. 16: 881-887 (1986).
MacDougall et al., "Detection of Ligand-Activated Conductive Ca.sup.21 Channels in Human B Lymphocytes," Cell 54: 229-234 (1988).
Fukishima et al., "Voltage-gated Ca.sup.2+ Channel in Mouse Myeloma Cells," Proc. Natl. Acad. Sci. U.S.A. 80: 2240-2242 (1983).
Dugas, "Human B Cell Activation: Selective Sensitivity of the Early Stages to Calcium Channel-Blocking Drugs," Eur. J. Immunol. 16: 162-167 (1986).
Tedder et al., "The B Cell Surface Molecule B1 is Functionally Linked with B Cell Activation and Differentiation," The Journal of Immunology 135: 973-979 (1985).
Tedder et al., "Isolation and Structure of a cDNA Encoding the Bl (CD20) Cell-Surface Antigen of Human B Lymphocytes," Proc. Natl. Acad. Sci. U.S.A. 85: 208-212 (1988).
Tedder et al., "Cloning of a Complementary DNA Encoding a New Mouse B Lumphocyte Differentiation Antigen, Homologous to the Human B1 (CD20) Antigen and Localization of the Gene to Chromosome 19," The Journal of Immunology 141: 4388-4394 (1988).
Tedder et al., "Phosphorylation of the B1 (CD20) Molecule by Normal and Malignmant Human B Lymphocytes," The Journal of Biological Chemistry 263: 10009-10015 (1988).

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