Antibody Synthesis In Transgenic Mice

During the ontogeny of B lymphocytes, progeny of a single cell can switch the constant (C) region isotype of the produced immunoglobulin (Ig) from IgM to IgG, IgA, or IgE, while maintaining the same variable (V) region. This process, referred to as heavy (H) chain class switching, is realized by a DNA rearrangement event called S-S recombination which occurs at the switch (S) region located in front of each C gene except for Cδ. S-S recombination can joxtapose the assembled V_h gene to the new, to be expressed C_H gene and delete the intervening C_h genes. This deletion model has got supports from numerous experiments involving myelomas, hybridomas, and normal B cells, especially the recent ones in which the circular DNA composed of the deleted sequence was isolated as a counter-product of the S-S recombination.On the other hand, analyses of B lymphocytes have also shown that some of the B cells can express more than one isotype simultaneously on the surface of a single cell, named double or multiple bearers. This phenomenon is not consistent with the above mentioned deletion model, because there is no DNA rearrangement at the C_h locus of the second, expressed isotype been detected in these cells. From the same reason, it is speculated that RNA procession might be responsible for the production of two or more C_h isotypes with same V region. Until now, at least the involvement of differential splicing of long RNA transcripts in the expression of IgM with IgD had been well elucidated.Recent results suggest that isotype class switching induced by some cytokines and polyclonal B cell activators in vitro is always preceded by transcription initiating from the 5' of each S region and emcompassing the downstream C_h gene. From this fact, we have proposed that trans-splicing...