CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation.
The 95 Kd CD19 antigen is the broadest lineage specific surface marker for B cells: it is present on the surface of virtually all B lymphocytes, including early B progenitor cells. In this study we have evaluated the function of the CD19 antigen by using the CD19 mAb HD37. Binding of HD37 mAb to B cells at low doses (0.5 microgram/ml) induced a strong inhibition of the proliferative response to anti-Ig. This inhibition was not mediated by the Fc portion of the antibody, since F(ab')2 fragments were as effective as the whole antibody. Both dose-response curve analysis and experiments in which a cross-linking second step anti-mouse antibody was added suggested that cross-linking of CD19 antigens was necessary for optimal inhibition. Early phases in B cell activation were affected by the HD37 mAb: it significantly reduced the number of cells that left G0 and entered the G1 phase of the cell cycle upon triggering with anti-mu. The increase in free intracellular ionized calcium [Ca2+]i that is induced by anti-mu was also consistently reduced by CD19 mAb. Cross-linking was also crucial for this effect, suggesting that a causal relationship may exist between the inhibition of anti-Ig-mediated [Ca2+]i fluxes and inhibition of proliferation. A variable but clear increase in [Ca2+]i levels followed cross-linking of CD19 antigens by specific mAb. This evidence suggests that CD19 molecules may function in the downregulation of B cell growth and proliferation.
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D002453:Cell Cycle; D002454:Cell Differentiation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D011947:Receptors, Antigen, B-Cell; D002118:Calcium