Historical background

Hybridoma production has as its background the joint application of two independently derived biological research tools. The first of these was the availability of induced monoclonal plasmacytomas in the mouse, for which Potter is primarily responsible. The availability of these lines and their ability to be transplanted in vivo and their subsequent adaptation to in vitro culture and fusion with normal B cells are described below. The second earlier-derived technology was that of cell fusion in which two somatic cells could be fused, resulting in the production of hybrid cells. The frequency of isolation of hybrid lines was then greatly facilitated by the use of selective media described by Littlefield, coupled with advances in the use of new fusion-inducing agents such as Sendai virus, lysolecithin and polyethylene glycol.

The origins of monoclonal antibody-producing hybridomas sprang from attempts to study immunoglobulin (Ig) gene expression and regulation in plasmacytoma cells. First, when two immunoglobulin-producing plasmacytomas were fused, both sets of immunoglobulin light and heavy chains continued to be expressed by the hybrid cells, resulting in 1) formation of hybrid molecules, 2) the failure of new immunoglobulin chains to be produced, and 3) that when a variant plasmacytoma that no longer expressed either of the wild-type light or heavy immunoglobulin chains was fused with an immuno-globulin-producing line, the nonproducer did not switch off immunoglobulin production by the other parental cell but continued to support the production of immunoglobulin from the other parent.

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