Differentiation in the I.29 B Cell Lymphoma: Precommitment to IgA or IgE Switch in Individual IgM+ Clones
Blymphocytes undergo during their development several sequential rearrangements at the immunoglobulin (Ig) loci (1). The first event is a D-JH recombination that usually takes place at both the heavy chain (IgH) loci, and is then followed by rearrangement of one of the numerous VHgenes to the DJHcomplex (2). When a functional VDJ rearrangement has taken place, synthesis of μ Polypeptide ensues and rearragments of the light chain loci begin. A K-λ hyerarchy has been demonstrated in both human and mouse B cells (3,4). A successful heavy chain gene recombination stops any further rearrangement at the IgH locus (5,6), and possibly stimulates IgL recombination. Similarly the creation of a productive light chain gene blocks further recombinations at the IgL loci (5). Subsequently IgM molecules are synthetized and expressed on the cell surface by lymphocytes (7). The latter may coexpress IgD through alternative splicing of the VDJ - Cμ -C δ transcription unit (8). IgM+ B cell may undergo a second recombinatorial event at the IgH locus, termed isotype switching. This event generally implies the deletion of Cμ, Cδ and all the CHgenes which are located 5′ to the one CH gene that will be expressed (9,10). Although the sequences mediating switch recombination have been isolated and determined (9–11), rather little is known about the mechanisms regulating isotype switching. The question of how an IgM+B lymphocyte decides which CH gene to recombine is still open. It is well known that certain antigens or routes of immunization result in vivo in the predominance of a given isotype (12). On the other hand several in vitro experiments have shown that more than one isotype can be produced by the progeny of a single B cell (13–15). Isotype switching is not the only differentiative option of an IgM+ B cell. The latter may infact respond to antigen or mitogen by differentiating into IgM secreting plasmacells (7). It is generally accepted that plasmacell may undergo a very limited number of divisions.
KeywordsClone 22C3 Switch Variant Plasmacell Differentiation Differentiative Potential Light Chain Locus
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