IMMUNOGLOBULIN GENES IN DIFFERENTIATING B CELLS

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A series of important changes in the structure of immunoglobulin (Ig) genes occurs during B cell development. Both formation of complete variable (V) regions 5' of the constant (C) regions encoding both heavy (H) and light chain proteins and the subsequent linkage of the V-H region with C-H regions 3' of C (heavy chain switching) occur by recombinatorial mechanisms. However, because these events are temporally distinct and use different recognition sequences, different recombinatorial systems are probably used in each case. To date, most of our information concerning the mechansim of H chain switching and its timing during the course of B cell differentiation has come from studies of myelomas and a few B cell tumors. We have recently developed a model system to study Ig gene structure during differentiation of mature B cells using the retrovirus Abelson virus. Using this approach, we have developed a series of clonal, immortalized, nontumorigenic mIgM and IgG-positive B cell lines. Different isolates synthesize various H and L chain isotypes and some isolates secrete Ig. The unique nature of these cells and their ability to carry out a key recombinatorial step in B cell development make them an ideal model system to study both the timing and the mechanism of deletional switching during B cell differentiation.