IMPAIRMENT OF ANTIGEN-SPECIFIC ANTIBODY-PRODUCTION IN TRANSGENIC MICEEXPRESSING A DOMINANT-NEGATIVE FORM OF GP130

gD130 is a common signal-transducing receptor component for the interl eukin 6 family of cytokines functioning in, for example, immune, hemat opoietic, and nervous systems. In this study, to investigate the physi ological functions of gD130 and to determine the pathological conseque nces of impaired gp130 signals, we have generated transgenic mice expr essing a cytoplasmically truncated form of mouse gp130. Expression of this form of gp130 in lymphocytes significantly suppressed interleukin 6-induced tyrosine phosphorylation of endogenous gD130 and a downstre am signaling molecule, signal transducer and activator of transcriptio n 3, indicating that this form has a dominant negative function, In sp ite of the impaired gp130 signals, the development of lymphocytes in t he transgenic mice appeared normal in terms of surface marker phenotyp es. These mice, however, exhibited severe defects in antigen-specific antibody production of most immunoglobulin isotypes other than IgM aft er immunization with 2,4-dinitrophenol-conjugated ovalbumin. These res ults demonstrate in vivo that gp130 is essential for antigen-specific antibody production.