Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes.
A panel of B cell-specific monoclonal antibodies that identify the CR2/EBV receptor were examined for their ability to mimic the T-independent mitogenic agent, EBV, and thus activate human peripheral blood B lymphocytes. Two of four different anti-CR2/EBV monoclonal antibodies, OKB7 and AB-1, produced a 50-fold to 200-fold dose-dependent stimulation of DNA synthesis of peripheral blood mononuclear cells. One of the other monoclonal antibodies, anti-B2, had slight activity, and the other, HB-5, was completely inactive. One of the mitogenic antibodies, OKB7, which directly inhibits binding and infection of B cells by EBV in the absence of a second anti-immunoglobulin antibody, was examined in further detail. Both the intact antibody in soluble form and its pepsin-derived F(ab')2 fragment stimulated DNA synthesis of unseparated B and T lymphocytes. Peak stimulation of DNA synthesis in peripheral blood mononuclear cells occurred between 4 to 6 days. B cells were responsible for incorporation of [3H]thymidine. However, T cells were required for activation of peripheral blood mononuclear cells by OKB7. OKB7, as well as the other mitogenic monoclonal anti-EBV/CR2 receptor antibody, also induced B cells to differentiate after 6 to 10 days of culture as indicated by polyclonal Ig secretion. IgM was the predominate immunoglobulin secreted. These studies thus indicate that certain epitopes on the EBV/CR2 receptor trigger B cells to divide and differentiate. This pathway of B cell activation, in contrast to that produced by EBV, is T cell dependent.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D002454:Cell Differentiation; D003176:Complement C3 / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D011951:Receptors, Complement / Q000378:metabolism*; D017464:Receptors, Complement 3d; D011991:Receptors, Virus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D003176:Complement C3; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D011991:Receptors, Virus; D004247:DNA