Abstract: Immunoglobulins (Ig) are expressed either on the surface of B cells or as secreted antibodies by plasma cells that represents the final stage of B cell differentiation. The present invention involves the use of antisense oligonucleotides (ASOs) for either reducing the production of the secreted form or either reducing the production of the membrane form. In particular, the inventors show that antisense oligonucleotides masking the secretory polyadenylation signal induce a decrease in the production of the secreted immunoglobulin. Inversely, antisense oligonucleotides masking the membrane polyadenylation signal induce a decrease in the production of the membrane-anchored immunoglobulin. The proof of concept has been obtained using an ASO hybridizing to the polyadenylation signal (PAS) sequence of the transcript encoding the secreted form of IgE. Indeed, the targeting of this PAS sequence induces a drastic decrease in IgE production.

Abstract: The invention relates to a transgenic non-human mammal comprising human immunoglobulin mu and epsilon heavy-chain constant transgenes C? and C? inserted in place of endogenous mu heavy-chain switch sequence S?, and its use for producing chimeric human immunoglobulin E antibodies specific for an antigen of interest.

Abstract: The invention relates to a transgenic non-human mammal comprising human immunoglobulin mu and epsilon heavy-chain constant transgenes C? and C? inserted in place of endogenous mu heavy-chain switch sequence S?, and its use for producing chimeric human immunoglobulin E antibodies specific for an antigen of interest.