Transgenic mice with mu and kappa genes encoding antiphosphorylcholine antibodies.

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Abstract
Transgenic mice were produced that carried in their germlines rearranged .kappa. and/or .mu. genes with V.kappa. and VH regions from the myeloma MOPC-167 .kappa. and H genes, which encode anti-PC antibody. The .mu. genes contain either a complete gene, including the membrane terminus (.mu. genes), or genes in which this terminus is deleted and only the secreted terminus remains (.mu. D mem genes). The .mu. gene without membrane terminus is expressed at as high level as the .mu. gene with the complete 3'' end, suggesting that this terminus is not required for chromatin activation of the .mu. locus or for stability of the mRNA. The transgenes are expressed only in lymphoid organs. In contrast to our previous studies with MOPC-21 .kappa. transgenic mice, the .mu. transgene is transcribed in T lymphocytes as well as B lymphocytes. Thymocytes from .mu. and .kappa..mu. transgenic mice display elevated levels of M-167 .mu. RNA and do not show elevated levels of .kappa. RNA, even though higher than normal levels of M-167 .kappa. RNA are detected in the spleen of these mice. .apprx. 60% of thymocytes of .mu. transgenic mice produce cytoplasmic .mu. protein. However, despite a large amount of .mu. RNA of the membrane form, .mu. protein cannot be detected on the surface of T cells, perhaps because it cannot associate with T cell receptor .alpha. or .beta. chains. Mice with the complete .mu. transgene produce not only the .mu. transgenic mRNA but also considerably increased amounts of .kappa. RNA encoded by endogenous MOPC-167 like .kappa. genes. This suggests that B cells are selected by antigen (PC) if they coexpress the .mu. transgene and appropriate anti-PC endogenous .kappa. genes. Mice with the .mu. D mem gene, however, do not express detectable levels of the endogeous MOPC-167 .kappa. mRNA. Like the complete .mu. transgene, the M-167 .kappa. transgene also causes amplification of endogenous MOPC-167 related immunoglobulins; mice with the .kappa. transgene have increased amounts of endogenous MOPC-167-like .mu. or .alpha. or .gamma. in the spleen, all of the secreted form. Implications for the regulation of immunoglobulin gene expression and B cell triggering are discussed.