A common mechanism for the synthesis of membrane and secreted immunoglobulin α, γ and μ chains

Abstract

Immunoglobulins serve as both secreted effector antibodies and antigen receptors bound to the membrane of lymphocytes. Each newly generated B lymphocyte expresses membrane IgM and subsequently co-expresses membrane IgM and membrane IgD. Antigen-driven clonal proliferation is accompanied by further differentiation with the generation of B lymphocytes expressing, in membrane-bound form, other classes and subclasses of immunoglobulin¹. Such memory cells are apparently capable of responding to antigen to generate further clones of cells secreting antibodies of particular classes and subclasses. The mechanism by which IgM functions as both a membrane-bound and a secreted immunoglobulin has been determined for both murine and human systems^2–4. The difference between the two forms of IgM is entirely at the C-terminus. The μ_s (secreted) chain has a hydrophilic peptide additional to the Cμ4 domain and the μ_m (membrane-bound) chain has a hydrophobic peptide replacing the hydrophilic C-terminal peptide of the μ_s chain^2–4. The μ_s and μ_m chains are translated from distinct mRNA molecules that are generated by alternative splicing and/or termination points of transcripts from a single rearranged μ gene^5,6. Recent evidence supports the existence of a similar mechanism for the generation of δ_s and δ_m chains^7–9. Structurally different γ_m and γ_s chains have been observed in human, mouse and chicken cells^10–12. The present study further distinguishes between γ_m and γ_s chains and characterizes the mRNA molecules encoding them in human cells. We have also characterized α_m and α_s chains in a human cell. The data reported here, together with other recent findings, suggest a common mechanism for the generation of membrane and secreted forms of α, γ and μ, chains.