Immunoglobulin Gene Rearrangement: Differential Signaling By a Transgenic Heavy Chain.
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Our body is the milieu for an ongoing battle between pathogen and antibody. The diversity of these foreign substances called antigens number in the thousands. Each has unique epitopes that act as keys to which the antibody binds. One explanation as to how the immune system is able to furnish such an assortment of antibodies to attack these antigens is V(D)J rearrangement. Antibodies consist of two heavy and two light chains, each with a variable and constant region. We have made transgenic mice with a human constant region and mouse variable region to study the signaling by the heavy chain during gene rearrangement in pre-B cells. The heavy chain typically rearranges first and then signals the light chain to rearrange. In our mice, however, the previously rearranged transgenic heavy chain inhibits rearrangement of the endogenous heavy chain but does not trigger light chain rearrangement. We believe this is because there are two distinct signals involved in V(D)J gene rearrangement, one to inhibit heavy chain rearrangement and another to induce light chain rearrangement. With the Abelson murine leukemia virus (A-MuLV), we hope to create immortalized B-cells in the pre-B stage expressing a transgenic heavy chain to compare them with hybridoma subclones in the B-cell stage that produce transgenic antibodies.