Failure of signaling through a chimeric class I-immunoglobulin molecule expressed on the surface of transfected B lymphoma cells and cells of transgenic mice.
To test the possibility that the crosslinkage of molecules expressing a transmembrane region derived from the membrane form of the mu immunoglobulin heavy chain would be sufficient for signal transduction in B cells, a chimeric gene (Kk-mu) consisting of extracellular exons of the class I gene H-2Kk and the transmembrane and cytosolic exons of the mu constant region gene was introduced into WEHI-231 B lymphoma cells and into mouse blastocysts. A protein consistent with the predicted product of the Kk-mu gene was expressed in a transfected cell clone (S18) and in transgenic mice. Crosslinkage of Kk-mu protein with soluble, Sepharose-bound, or dextran-conjugated anti-H-2Kk antibodies failed to induce the accumulation of inositol phosphates or to elevate intracellular calcium concentrations in either S18 cells or B lymphocytes from transgenic mice. Furthermore, crosslinkage of Kk-mu did not inhibit growth of S18 cells or stimulate DNA synthesis by transgenic B cells, in the presence or absence of interleukin-4. The failure of crosslinkage of Kk-mu to initiate detectable intracellular biochemical change or to effect cellular growth suggests that simple crosslinkage of molecules expressing the mu transmembrane region is not sufficient to transduce signals in B cells.
Tsang
W K
WK
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Mizuguchi
J
J
Ishida
Y
Y
Watson
C
C
Chused
T
T
Inman
J
J
Margulies
D H
DH
Paul
W E
WE
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D005803:Genes, Immunoglobulin; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007075:Immunoglobulin M / Q000235:genetics / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007075:Immunoglobulin M; D007295:Inositol Phosphates; D011947:Receptors, Antigen, B-Cell; D002118:Calcium