B Cells, Hormonal Immunity, and Monoclonal Antibodies operating in concert with one another and with phagocytic cells (macrophages). These cellular interactions include both direct cognate interactions involving cell-to-cell contact and cellular interactions involving the secretion of and response to cytokines or lymphokines. Lymphoid cells are found in lymphoid tissues, such as lymph nodes or spleen, or in the peripheral circulation. The cells that make up the immune system originate from stem cells in the bone marrow.
B lymphocytes synthesize and secrete antibodies. Mature, antigen-responsive B cells develop from pre-B cells (committed B-cell progenitors) and differentiate to become plasma cells, which produce large quantities of antibodies. Pre-B cells originate from bone marrow stem cells in adults after rearrangement of immunoglobulin genes from their germ cell configuration. Mature B cells express cell surface immunoglobulin molecules that function as receptors for antigen.
Upon interaction with antigen, mature B cells respond to become antibody-producing cells.
The process requires the presence of appropriate cell–cell stimulatory signals and cytokines. Monoclonal antibodies are directed against a specific antigenic determinant. In contrast, polyclonal antibodies detect multiple epitopes that might be presented by just one or a panel of proteins. The in vitro production of monoclonal antibodies, pioneered by Kohler and Milstein in the 1970s, has become an invaluable diagnostic and therapeutic tool, particularly for the management of malignancies (76). The tumor antigen CA125, for example, was detected in a screen of antibodies generated against ovarian cancer cell lines. A radioimmunoassay is widely used to measure CA125 in the serum of patients with ovarian cancer and guide treatment decisions. Therapeutic approaches utilized immunotoxin-conjugated monoclonal antibodies directed to human ovarian adenocarcinoma antigens. These antibodies induce tumor cell killing and can prolong survival in mice implanted with a human ovarian cancer cell line. However, some obstacles limit the clinical use of monoclonal antibodies, including tumor cell antigenic heterogeneity, modulation of tumor-associated antigens, and cross-reactivity of normal host and tumor-associated antigens. No unique tumor-specific antigens were identified. All tumor antigens have to be considered as tumor-related antigens because they are expressed on the malignant as well as the nonmalignant tissues. Because most monoclonal antibodies are murine, the host’s immune system can recognize and respond to these foreign mouse proteins. The use of the genetically engineered monoclonal antibodies composed of human-constant regions with specific antigen-reactive murine variable regions can result in reduced antigenicity.
T lymphocytes have a central role in the generation of immune responses by acting as helper cells in both humoral and cellular immune responses and by acting as effector cells in cellular responses. T-cell precursors originate in bone marrow and move to the thymus, where they mature into functional T cells. During their thymic maturation, T cells that can recognize antigen in the context of the major histocompatibility complex (MHC) molecules are selected, while self-responding T cells are removed (75).