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M J Shulman

Publications and source records attributed to M J Shulman.

76 records · Page 5Linked to original sources
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Transfer of a cloned immunoglobulin light-chain gene to mutant hybridoma cells restores specific antibody production.

The expression of immunoglobulin (Ig) genes is regulated at several levels. For example, although kappa-chain production requires a DNA rearrangement that juxtaposes variable and joining segments, this rearrangement is not sufficient for kappa-chain gene expression; that is, some cell types do not permit immunoglobulin production. The mechanisms responsible for the regulation of the expression of rearranged immunoglobulin genes are poorly understood. The technique of modifying cloned genes in vitro and transferring the modified genes to cells in culture provides a tool for identifying the structural features required for gene expression. To analyse immunoglobulin genes in this manner, however, it is first necessary to use, as recipients, cells that normally permit immunoglobulin production. We report here that a cloned kappa-chain gene is expressed in immunoglobulin-producing hybridoma cells. Furthermore, the product of the transferred kappa-chain gene is capable of restoring specific antibody production to the transformed cells.

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Production of functional chimaeric mouse/human antibody.

The availability of monoclonal antibodies has revived interest in immunotherapy. The ability to influence an individual's immune state by administering immunoglobulin of the appropriate specificity may provide a powerful approach to disease control and prevention. Compared with immunoglobulin from other species, human immunoglobulin (Ig) might be best for such therapeutic intervention; it might function better with the recipient's effector cells and should itself be less immunogenic. The success of the mouse hybridoma system suggests that immunoglobulin of virtually any specificity can be obtained from a properly immunized animal. In the human system, however, immunization protocols are restricted by ethical considerations, and it is not yet clear whether human antibody-producing cell lines of the required specificity can be obtained from adventitiously immunized individuals or from in vitro immunized cells. A method which might circumvent these difficulties is to produce antibodies consisting of mouse variable regions joined to human constant regions. Therefore, we have constructed immunoglobulin genes in which the DNA segments encoding mouse variable regions specific for the hapten trinitrophenyl (TNP) are joined to segments encoding human mu and kappa constant regions. These 'chimaeric' genes are expressed as functional TNP-binding chimaeric IgM. We report here some of the properties of this novel IgM.

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