A hybridoma cell is a hybrid of two other cell types, called B lymphocytes and myeloma cells. When a B lymphocyte and a myeloma cell are hybridized, they form a hybridoma cell which is capable of producing monoclonal antibodies. When antibodies are monoclonal, it means all the antibodies in a given sample have come from the same B lymphocyte, and are all identical. Monoclonal antibodies have a wide range of uses, including in diagnostic medicine, and biological research.
B lymphocytes are the antibody-producing cells of the immune system. The cells and the antibodies they produce are essential for providing protection against bacterial infection, as well as infection with certain types of viruses. B lymphocytes produce specific antibodies, but they have a limited lifespan. A myeloma cell is a B lymphocyte which has turned malignant, and is therefore a cancer cell. Myeloma cells cannot produce antibodies, but are able to continue dividing in a cell culture indefinitely.
The process for developing hybridoma cells was invented in the 1970s. To begin this process, a mouse is immunized with a protein antigen. The mouse will then mount an immune response to the antigen, which will include B lymphocytes making antibodies which recognize the antigen. Next, the spleen of the immunized mouse is removed, and B lymphocytes are isolated from the spleen tissue.
The antibody-producing B lymphocytes are then cultured with myeloma cells. The culture of cells is treated with a chemical that makes cell membranes permeable, meaning they are punctuated with tiny holes. This allows the myeloma cells and B lymphocytes to fuse more readily. When a B lymphocyte fuses with a myeloma cell, the result is a hybridoma cell. The next step is to isolate the newly-fused cells so that each cell is in its own separate culture. This is necessary to ensure that antibodies produced by the cells are monoclonal, and are not contaminated with antibodies from different cells.
Finally, hybridoma cells are selected for culture based on how well they recognize the antigen that was used to immunize the mouse at the beginning of the process. This is important, as B lymphocytes do not all produce exactly the same type of antibody, even when they were immunized by the same antigen. Each B lymphocyte produces antibodies that recognize the antigen with differing degrees of specificity and strength; therefore a further selection process is used to single out the antibody-producing cells with the desired responses.
The ability to use hybridomas to generate monoclonal antibodies to virtually any protein makes them an extremely useful scientific tool. Monoclonal antibodies are used extensively in biological research to identify and isolate cellular proteins. In diagnostic medicine, monoclonal antibodies are an effective diagnostic tool because they can be used to detect bacterial, virus, or tumor antigens which are present in even small quantities in a blood or tissue sample.