The role of the transferrin receptor in human B lymphocyte activation.
Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. T cells demonstrate a functional requirement for transferrin receptors in the activation process. These receptors, in turn, are induced to appear by T cell growth factor (interleukin 2). In the experiments reported here, we examined the regulation of transferrin receptor expression on activated human B cells and whether these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B cell growth factor). This expression is required for proliferation to occur, because antibody to transferrin receptor (42/6) blocks B cell proliferation. Induction of immunoglobulin secretion, however, although dependent on phytohemagglutinin-treated T cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by anti-transferrin receptor antibody. These findings support a model for B cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B cell growth factor and transferrin receptor expression, for proliferation; and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.
D000911:Antibodies, Monoclonal / Q000502:physiology; D000921:Antibody-Producing Cells / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D011990:Receptors, Transferrin; D013209:Staphylococcal Vaccines / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006133:Growth Substances; D007075:Immunoglobulin M; D008222:Lymphokines; D010835:Phytohemagglutinins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D013209:Staphylococcal Vaccines; D015847:Interleukin-4; D013936:Thymidine