The MA were produced for the first time by Kholer and Milstein in 1975, who were awarded the Nobel Prize for Medicine in 1984 for their discovery. They managed to fuse two cells and obtain a hybrid (Hybridoma) which had functional characteristics of both cell populations. They fused a B lymphocyte from the spleen of a mouse immunized with sheep erythrocytes which produced antibodies against an erythrocyte epitope, with mouse myeloma cells that lived indefinitely "in vitro". They obtained a hybrid that was able to permanently secrete immunoglobulins against the sheep erythrocyte epitope, as the hybridoma had also acquired the capacity to secrete myeloma immunoglobulins and the ability to live "in vitro". In other words, they managed to produce antibodies "in vitro" against a single determinant of a complex antigen structure.

This diagram represents in graphic form the production of an hybridoma through fusion between a B lymphocyte and a myeloma cell for the production of monoclonal antibodies.