ABSTRACT
Immunoglobulin expression and B lymphocyte differentiation are intimately linked. Immunoglobulin heavy chains are encoded by four groups of gene segments called the DH (diversity), JH (joining), CH (constant), and VH (variable) region segments that undergo rearrangement to allow transcription through one VDJ segment resulting in expression of a full length protein (reviewed in Papavasiliou et al., 1997). Rearrangement occurs in an ordered fashion during differentiation so that D segments first become juxtaposed with J segments (the pro-B cell stage), and then V segments rearrange with the DJ segments to form one contiguous exon (the pre-B cell stage). Rearrangement and expression of the light chain genes defines the next stage in B cell differentiation (the immature B cell stage). Mice that do not produce the proteins required for rearrangement are unable to express immunoglobulin heavy chains or to produce B lymphocytes representative of stages beyond early pro-B cells (Shinkai et al., 1992; Schatz et al., 1989). Later pro-B and pre-B stages in B cell differentiation are at least partially defined on the basis of the rearrangement status of the heavy chain genes. Differentiation beyond the pre-B cell stage also requires rearrangement, but of a light chain locus. Thus, expression of rearranged heavy chains in recombinase deficient mice results in blocks in differentiation at the pre-B cell stage (Young et al., 1994). Signaling through surface receptors containing the heavy chain in conjunction with pseudo-light chains in the pre-B cell, or with light chains in the mature B cell, is critical for progression through B cell differentiation (Burrows and Cooper, 1997; Tarlinton et al., 1997). Therefore, appropriate expression of immunoglobulin heavy chains is also important for late stages in B cell differentiation leading up to the production and secretion of antibody. Although many of the details of the rearrangement process are now understood, this chapter will focus on additional events important for transcription of the heavy chain locus.
