EXPRESSION OF CD14 CORRECTS THE SLOW RESPONSE TO LIPOPOLYSACCHARIDE IN THE 1B8 MUTANT OF THE B-CELL LYMPHOMA 70Z 3/

B cells and macrophages both activate NF-kappa B/Rel in response to li popolysaccharide (LPS), but differ in sensitivity to EPS and in downst ream genes that are activated. CD14 is a high-affinity receptor for LP S found on macrophages, but not B cells. We expressed human CD14 (hCD1 4) in the mouse B lymphoma, 70Z/3, and a mutant, 1B8, which responds s lowly to LPS, to test whether expression of hCD14, could correct or by pass the defect in 1B8 cells. We compared the timing and extent of kno wn responses to LPS in 70Z/3 cells and the 1B8 mutants. The hCD14(+) 1 B8 and 70Z/3 cells responded more rapidly and were sensitive to 100-fo ld lower levels of LPS than their untransfected counterparts., Degrada tion of the 1 kappa B-alpha and -beta molecules and translocation of t he NF-kappa B/Rel complexes into the nucleus were more rapid and the s teady-state levels of Igk mRNA and mIgM on the cell surface were marke dly increased in cells that expressed hCD14., The LPS response of the hCD14(+) 1B8 and 70Z/3 cells showed subtle differences, In the 1B8 hCD 14 cells, the p50/p50 complexes were never abundant in nuclear extract s, and degradation of I kappa B-beta was slower than in hCD14 70Z/3 ce lls. This partial correction of the 1B8 phenotype suggests that the de fective component In 1B8 participates in the CD14 signaling pathway an d could include ii-re B-cell LPS receptor itself.