progeny differentiate into plasma cells producing IgM antibodies, whereas others undergo class switching to express transmembrane immunoglobulins of a different class, followed by the production of secreted antibody of the new class. The membrane-bound forms of all immunoglobulin classes are monomers comprising two heavy and two light chains. IgM and IgA polymerize only when they have been secreted. The membrane-bound form of immunoglobulin heavy chain has at the carboxy terminus a hydrophobic transmembrane domain of about 25 amino acid residues that anchors it to the surface of the B lymphocyte. The secreted form replaces this transmembrane domain with a carboxy terminus composed of a hydrophilic secretory tail. These two forms of carboxy termini are encoded by different exons found at the end of each CH  gene as these exons undergo alternative RNA processing.
For example, the IgM heavy-chain gene contains four exons—Cμ1 to Cμ4— that encode its four heavy-chain Ig domains (Fig. 5.22). The end of the Cμ4 exon also encodes the carboxy terminus for the secreted form. Two additional downstream exons, M1 and M2, encode the transmembrane forms. If the primary transcript is cleaved at the polyadenylation site (pAs) located just downstream of the Cμ4 exon but before the last two exons, then only the secreted molecule can be produced. If the polymerase transcribes through this first polyadenylation site, then splicing can occur from a non-consensus splice-donor site within the Cμ4 exon to the M1 exon. In this case, polyadenylation occurs at a downstream site (pAm) and the cell-surface form of immunoglobulin can be produced. This alternative splicing is incompletely understood, but
AAA AAA L VDJ C˜1 C˜2 C˜3 C˜4SCpAs pAmM1 M2 carboxy terminusfor transmembrane IgM carboxy terminusfor secreted IgM AAA AAA Rearranged DNA mRNA Protein Transcription Different forms of RNA processing Translation, protein processing Primary transcript RNA Secreted IgMTransmembrane  IgM L VDJ C˜1 C˜2 C˜3 C˜4SC pAs pAmM1 M2
Fig. 5.22 Transmembrane and secreted forms of immunoglobulins are derived from the same heavy-chain sequence by alternative RNA processing. At the end of the heavy-chain C gene, there are two exons (M1 and M2, yellow) that together encode the transmembrane region and cytoplasmic tail of the transmembrane form. Within the last C-domain exon, a secretion-coding (SC) sequence (orange) encodes the carboxy terminus of the secreted form. In the case of IgD, the SC sequence is in a separate exon (not shown), but for the other isotypes, including IgM as shown here, the SC sequence is contiguous with the last C-domain exon. The events that dictate whether a heavy-chain RNA will result in a secreted or a transmembrane immunoglobulin occur during processing of the pre-mRNA transcript. Each heavy-chain C gene has two potential polyadenylation sites (shown as pAs and pAm). Left panel: the transcript is cleaved and polyadenylated (AAA) at the second site (pAm). Splicing occurs from a site located within the last Cμ4 exon just upstream of the SC sequence (orange), to a second site at the 5ʹ end of the M1 exons (yellow). This results in removal of the SC sequence and joining of the Cμ4 exon to the exons M1 and M2 and generates the transmembrane form of the heavy chain. Right panel: polyadenylation occurs at the first poly(A) addition site (pAs), and transcription terminates before the exons M1 and M2, preventing the generation of the transmembrane form of the heavy chain, and producing the secreted form.