Immunochemical evidence that human apoB differs when expressed in rodent versus human cells

LDL from human apolipoprotein B-100 (apoB-100) transgenic (HuBTg+/+) mice contains more triglyceride than LDL from normolipidemic subjects. To obtain novel monoclonal antibody (MAb) probes of apoB conformation, we generated hybridomas from HuBTg+/+ that had been immunized with LDL isolated from human plasma. One apoE-specific and four anti-apoB-100-specific hybridomas were identified. Two MAbs, 2E1 and 3D11, recognized an epitope in the amino-terminal 689 residues of apoB in native apoB-containing lipoproteins (LpBs) from human plasma or from the supernatant of human hepatoma HepG2 cells, but did not react with LpB from HuBTg+/+ mice or LpB secreted by human apoB-100-transfected rat McArdle 7777 hepatoma cells. 2E1 reacted weakly and 3D11 reacted strongly with apoB from HuBTg+/+ mice after SDS-PAGE. The lack of expression of the 2E1 and 3D11 epitopes on native LpB from HuBTg+/+ mice did not solely reflect the abnormal lipid composition of murine LpB. Both epitopes were detected in all human plasma samples tested and in all human plasma LpB classes.Therefore, human apoB expressed by rodent hepatocytes or hepatoma cells appears to adopt a different conformation or undergoes different posttranslational modification than apoB expressed in human hepatocytes or hepatoma cells. LDL from human apolipoprotein B-100 (apoB-100) transgenic (HuBTg+/+) mice contains more triglyceride than LDL from normolipidemic subjects. To obtain novel monoclonal antibody (MAb) probes of apoB conformation, we generated hybridomas from HuBTg+/+ that had been immunized with LDL isolated from human plasma. One apoE-specific and four anti-apoB-100-specific hybridomas were identified. Two MAbs, 2E1 and 3D11, recognized an epitope in the amino-terminal 689 residues of apoB in native apoB-containing lipoproteins (LpBs) from human plasma or from the supernatant of human hepatoma HepG2 cells, but did not react with LpB from HuBTg+/+ mice or LpB secreted by human apoB-100-transfected rat McArdle 7777 hepatoma cells. 2E1 reacted weakly and 3D11 reacted strongly with apoB from HuBTg+/+ mice after SDS-PAGE. The lack of expression of the 2E1 and 3D11 epitopes on native LpB from HuBTg+/+ mice did not solely reflect the abnormal lipid composition of murine LpB. Both epitopes were detected in all human plasma samples tested and in all human plasma LpB classes. Therefore, human apoB expressed by rodent hepatocytes or hepatoma cells appears to adopt a different conformation or undergoes different posttranslational modification than apoB expressed in human hepatocytes or hepatoma cells. Lipoproteins containing apolipoprotein B-100 (apoB-100) (LpBs) are complex macromolecular structures that vary in size, hydrated density, electrophoretic mobility, and lipid and apolipoprotein composition. The physical and chemical heterogeneity modulates the conformation of apoB-100 and, as a consequence, its function (1Aviram M. Lund-Katz S. Phillips M.C. Chait A. The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprrotein B-100 with cells.J. Biol. Chem. 1988; 263: 16842-16848Google Scholar, 2Galeano N.F. Milne R. Marcel Y.L. Walsh M.T. Levy E. Nguyen T.D. Gleeson A. Arad Y. Witte L. Al-Haideri M. Rumsey S.C. Deckelbaum R.J. Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.J. Biol. Chem. 1994; 269: 511-519Google Scholar, 3McNamara J.R. Small D.M. Li Z.L. Schaefer E.J. Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B.J. Lipid Res. 1996; 37: 1924-1935Google Scholar, 4McKeone B.J. Patsch J.R. Pownall H.J. Plasma triglycerides determine low density lipoprotein composition, physical properities, and cell-specific binding in cultured cells.J. Clin. Invest. 1993; 91: 1926-1933Google Scholar, 5Chen G.C. Liu W. Duchateau P. Allaart J. Hamilton R.L. Mendel C.M. Lau K. Hardman D.A. Frost P.H. Malloy M.J. Kane J.P. Conformational differences in human apolipoprotein B-100 among subspecies of low density lipoproteins (LDL). Association of altered proteolytic accessibility with decreased receptor binding of LDL subspecies from hypertriglyceridemic subjects.J. Biol. Chem. 1994; 269: 29121-29128Google Scholar, 6Kleinman Y. Eisenberg S. Oschry Y. Gavish D. Stein O. Stein Y. Defective metabolism of hypertriglyceridemic low density lipoproteins in cultured human skin fibroblasts.J. Clin. Invest. 1985; 75: 1796-1803Google Scholar). LDLs in human apoB-100 transgenic (HuBTg+/+) mice are enriched in triglyceride (TG) compared with LDL in human plasma (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar). The metabolic basis for the abnormal LDL composition in the HuBTg+/+ mice is unclear (8McCormick S.P.A. Ng J.K. Véniant M. Borén J. Pierotti V. Flynn L.M. Grass D.S. Connolly A. Young S.G. Transgenic mice that overexpress mouse apolipoprotein B - Evidence that the DNA sequences controlling intestinal expression of the apolipoprotein B gene are distant from the structural gene.J. Biol. Chem. 1996; 271: 11963-11970Google Scholar, 9Grass D.S. Saini U. Felkner R.H. Wallace R.E. Lago W.J.P. Young S.G. Swanson M.E. Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normal humans.J. Lipid Res. 1995; 36: 1082-1091Google Scholar, 10Kim E. Young S.G. Genetically modified mice for the study of apolipoprotein B.J. Lipid Res. 1998; 39: 703-723Google Scholar). Because anti-apoB monoclonal antibodies (MAbs) can be sensitive probes of apoB conformation (1Aviram M. Lund-Katz S. Phillips M.C. Chait A. The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprrotein B-100 with cells.J. Biol. Chem. 1988; 263: 16842-16848Google Scholar, 2Galeano N.F. Milne R. Marcel Y.L. Walsh M.T. Levy E. Nguyen T.D. Gleeson A. Arad Y. Witte L. Al-Haideri M. Rumsey S.C. Deckelbaum R.J. Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.J. Biol. Chem. 1994; 269: 511-519Google Scholar, 4McKeone B.J. Patsch J.R. Pownall H.J. Plasma triglycerides determine low density lipoprotein composition, physical properities, and cell-specific binding in cultured cells.J. Clin. Invest. 1993; 91: 1926-1933Google Scholar, 5Chen G.C. Liu W. Duchateau P. Allaart J. Hamilton R.L. Mendel C.M. Lau K. Hardman D.A. Frost P.H. Malloy M.J. Kane J.P. Conformational differences in human apolipoprotein B-100 among subspecies of low density lipoproteins (LDL). Association of altered proteolytic accessibility with decreased receptor binding of LDL subspecies from hypertriglyceridemic subjects.J. Biol. Chem. 1994; 269: 29121-29128Google Scholar, 11Kinoshita M. Krul E.S. Schonfeld G. Modification of core lipids of low density lipoproteins produces selective alterations in the expression of apoB-100 epitopes.J. Lipid Res. 1990; 31: 701-708Google Scholar, 12Wang X. Pease R. Bertinato J. Milne R.W. Well-defined regions of apolipoprotein B-100 undergo conformational change during its intravascular metabolism.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1301-1308Google Scholar), we hypothesized that anti-apoB MAbs could be specifically generated that could detect structural differences between LpB synthesized by humans and HuBTg+/+ transgenic mice. Interspecies immunization generally results in the production of antibodies against species-specific epitopes that rarely discriminate between polymorphic forms of the antigen. In contrast, intraspecies immunization preferentially elicits an immune response against allogeneic or polymorphic epitopes. An example of the latter is the Ag-system of human apoB polymorphism that was originally defined by antibodies in the sera of multitransfused individuals and multiparous women (13Butler R. Polymorphisms of the human low-density lipoproteins.Vox Sang. 1967; 12: 2-17Google Scholar). Similarly, the complex apoB polymorphisms of swine were identified with antibodies generated by allogeneic immunization (14Rapacz J. Hasler-Rapacz J. Taylor K.M. Checovich W.J. Attie A.D. Lipoprotein mutations in pigs are associated with elevated plasma cholesterol and atherosclerosis.Science. 1986; 234: 1573-1577Google Scholar). While intraspecies immunization may be the protocol of choice for the production of antibodies specific for polymorphic epitopes in animals, ethical and technical limitations preclude its use in humans. The availability of HuBTg+/+ mice now offers the possibility for developing a strategy that simulates the conditions of intraspecies immunization while maintaining the advantages of using animals for immunization. Here we demonstrate that MAbs generated with spleen cells of HuBTg+/+ mice that had been immunized with human LDL can detect differences in the conformation or posttranslational modification between human apoB secreted by humans and mice. LDLs were prepared from plasma of healthy donors (Canadian Red Cross) or patients with familial defective apoB (FDB) who were heterozygous for the apoB-100Arg3500→Gln allele (Lipid Clinic of the Institut de Recherches Cliniques de Montréal). The plasma was supplemented immediately with EDTA (1.0 mM), sodium azide (0.02%), phenylmethanesulfonal fluoride (0.5 mM), aprotinin (1 μg/ml), and butylated hydroxytoluene (20 nM). LDLs (1.019–1.063 g/ml) were isolated by sequential ultracentrifugation at 40,000 rpm for 18 h in a Beckman L5-65 ultracentrifuge with a 50.2 Ti rotor (Beckman Instruments, Palo Alto, CA) (15Havel R.J. Eder H.A. Bragdon J.H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.J. Clin. Invest. 1955; 34: 1345-1353Google Scholar). Solvent densities were adjusted with KBr. The isolated LDL were dialyzed against phosphate-buffered saline (PBS) (pH 7.4) containing 1 mM EDTA and 0.02% NaN3, sterilized by ultrafiltration, and stored at 4°C in the dark. LpBs were isolated from mouse plasma by ultracentrifugation at 100,000 rpm for 3 h at a density of 1.063 g/ml in a Beckman Optima TL table-top ultracentrifuge. After centrifugation, the d < 1.063 g/ml fraction was removed and dialyzed as above. The production and characterization of HuBTg+/+ (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar), human apoB-100Arg3500→Gln (HuBR3500QTg+/+) (16Borén J. Lee I. Zhu W.M. Arnold K. Taylor S. Innerarity T.L. Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100.J. Clin. Invest. 1998; 101: 1084-1093Google Scholar), and human hepatic lipase human apoB (HuHLTg+/−HuBTg+/−) (17Braschi S. Couture N. Gambarotta A. Gauthier B.R. Coffill C.R. Sparks D.L. Maeda N. Schultz J.R. Hepatic lipase affects both HDL and ApoB-containing lipoprotein levels in the mouse.Biochim. Biophys. Acta. 1998; 1392: 276-290Google Scholar) transgenic mouse lines have been described. Human apoB-100 human cholesteryl ester transfer protein (CETP) transgenic mice (HuBTg+/−, HuCETPTg+/−) were purchased from Taconic (Germantown, NY). LDL receptor knockout (LDLr−/−) mice (Jackson Laboratory, Bar Harbor, ME) were bred with human HuBTg+/+ mice to obtain HuBTg+/+LDLr−/− mice. The HuBTg+/+ mice (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar) were immunized by intraperitoneal injection of normal or FDB LDL (100 μg) in 200 μl of PBS containing 50 μg of the immunological adjuvant N-acetylmuramyl-l-alanyl-d-isoglutamine (Calbiochem, La Jolla, CA). The mice received at least two additional identical boosts at 3-week intervals. Serum antibody titers were monitored 1 week after each boost by a solid-phase radioimmunometric assay (RIA) with normal or FDB LDL as the immobilized antigen. Four days before the fusion and at least 3 weeks after the last boost, a final boost (50 μg of LDL in 100 μl of PBS) was administered by tail vein injection. The fusion of splenocytes from immunized mice with SP2-0 plasmacytoma cells has been described (18Milne R.W. Weech P.K. Marcel Y.L. Immunological for and lipoproteins and E. Lipoprotein Scholar). to days after the the of the of the were tested for the of antibodies by a solid-phase In the were by a hybridomas were by as described (18Milne R.W. Weech P.K. Marcel Y.L. Immunological for and lipoproteins and E. Lipoprotein Scholar). The of apoB MAbs that and and the apoB-100 have been described X. Pease R. Bertinato J. Milne R.W. Well-defined regions of apolipoprotein B-100 undergo conformational change during its intravascular metabolism.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1301-1308Google Scholar, R.J. Milne R.W. A. P. Marcel Y.L. J. of expression to the epitopes for a of monoclonal antibodies against apolipoprotein Biol. Chem. Scholar, Flynn L.M. Véniant E. M. P. L.M. Young S.G. of monoclonal antibodies specific for mouse apolipoprotein B-100 in apolipoprotein Lipid Res. Scholar). The solid-phase and solid-phase have been described (18Milne R.W. Weech P.K. Marcel Y.L. Immunological for and lipoproteins and E. Lipoprotein Scholar, Y.L. M. Weech P.K. Milne R.W. of on human apolipoprotein conformational for Biol. Chem. Scholar). To changes in apoB conformation that can LDLs are to we with a solid-phase The of (50 μl at in mM that is specific for an epitope between residues and of human apoB R.J. Milne R.W. A. P. Marcel Y.L. J. of expression to the epitopes for a of monoclonal antibodies against apolipoprotein Biol. Chem. Scholar) was to by an at was and the were with mM containing and with in PBS for The was and supernatant (50 was After a h the were with and for h with 50 μl of in After with was in a The assay to determine between antibodies for binding to immobilized LDL has been described R.J. Milne R.W. A. P. Marcel Y.L. J. of expression to the epitopes for a of monoclonal antibodies against apolipoprotein Biol. Chem. Scholar). MAbs were from or from of mice by on C.R. of and from mouse using Scholar). The of from MAbs has been described R.W. R. Marcel Y.L. of monoclonal antibodies against human low density Scholar). The and antibodies were as described (18Milne R.W. Weech P.K. Marcel Y.L. Immunological for and lipoproteins and E. Lipoprotein Scholar). The specific activity of was of Lipoproteins were to Beckman and to to the Lipoproteins were to and to J. transfer of from to and Scholar). The were for human transgenic and mouse apoB with MAbs specific for human R.J. Milne R.W. A. P. Marcel Y.L. J. of expression to the epitopes for a of monoclonal antibodies against apolipoprotein Biol. Chem. Scholar, R.W. R. Marcel Y.L. of monoclonal antibodies against human low density Scholar) or mouse Flynn L.M. Véniant E. M. P. L.M. Young S.G. of monoclonal antibodies specific for mouse apolipoprotein B-100 in apolipoprotein Lipid Res. Scholar) apoB and as described R.J. Milne R.W. A. P. Marcel Y.L. J. of expression to the epitopes for a of monoclonal antibodies against apolipoprotein Biol. Chem. Scholar). of apoB secreted from McArdle 7777 rat hepatoma cells M.F. Taylor Young S.G. B.J. of forms of human apolipoprotein B in rat hepatoma cells. Evidence that the of apolipoprotein B has a on the density of the secreted Biol. Chem. Scholar), human LpB from were with a apoB K. Y. The of low density lipoproteins in rat hepatoma cells is by Biol. Chem. 2000; Scholar) before to and electrophoretic transfer to The were with mouse anti-apoB MAbs and by after with was by a modified S. modification of the to protein in and lipoprotein Scholar) with as a protein boosts with human immunization of HuBTg+/+ mice a immune response in the and specific hybridomas were from One secreted an that was specific for an epitope in the of human The four hybridomas secreted MAbs, of could between LDL isolated from normal and LDL isolated from FDB subjects. of the MAbs were specific for epitopes expression was or by the Two of the anti-apoB MAbs were to react with epitopes that are LpBs are immobilized on a The characterization of latter MAbs is not described compared the of the two MAbs, 2E1 and 3D11, with normal human LDL and LpB from HuBTg+/+ and mice. Both reacted with human LDL but with lipoproteins from or mice the anti-apoB-100-specific reacted with both the human LDL and LpB of the human apoB transgenic mice The of were with of lipoproteins that had been separated by The MAbs were tested for with lipoproteins that had been separated by and to 2E1 reacted strongly with human apoB-100 and weakly with human transgenic 3D11 reacted strongly with the of MAbs for human LDL that was in the solid-phase and after was not after The apoB MAbs and recognized both human apoB-100 and human transgenic of the MAbs recognized mouse of lipoproteins with to of apoB before did not apoB the of the antibodies were the the was or conditions To determine the MAbs transgenic LpBs that were not to we tested LpB samples for to with immobilized human LDL for binding to MAbs in a solid-phase Human LDL and transgenic LpB for binding to human LDL and not transgenic LpB for binding to MAbs 2E1 and and isolated from human plasma for binding to both 2E1 and 3D11 Lipoproteins isolated from mice were with all of the The lack of of MAbs 2E1 and 3D11 with human apoB expressed in human apoB transgenic mice could from apoB polymorphism different posttranslational modification of apoB in the transgenic mice and or altered apoB conformation in the LpB of the transgenic mice To the 2E1 and 3D11 epitopes were expressed in different we tested plasma samples from normolipidemic for with MAbs 2E1 and 3D11 and with the anti-apoB in a of the plasma samples with the immobilized LDL for binding the 2E1 and 3D11 MAbs results were with an additional that were tested The 2E1 and 3D11 epitopes were detected on LpB from human apoB transgenic mice after SDS-PAGE. The lack of with the native LpB from the HuBTg+/+ mice could reflect an altered conformation to the physical and chemical of the LpBs that in the transgenic mice. with LDLs in normolipidemic the LDLs in HuBTg+/+ mice are (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar), low hepatic lipase activity and the lack of CETP activity in plasma. the 2E1 and 3D11 of LpB from human mice and from mice by a solid-phase The of the human hepatic lipase or the human CETP the HuBTg+/+ did not in expression of the 2E1 and 3D11 epitopes on the transgenic LpB of LpB from the mice with plasma of mice did not to expression of the two epitopes. The cholesteryl LDL of mice to react with the 2E1 and 3D11 antibodies The HepG2 human hepatoma apoB-100 on the LpBs of HuBTg+/+ are and have a hydrated density similar to that of LDL K. Borén J. M. A. G. O. P. on the of lipoproteins in HepG2 cells.J. Biol. Chem. 1988; 263: Scholar). the 2E1 and 3D11 of LpB secreted from HepG2 cells. The LpB in the HepG2 with LDL isolated from human plasma for binding to both antibodies In contrast, the LpB secreted by human apoB-100-transfected rat hepatoma cells B.J. An expression for human apolipoprotein B100 in a rat hepatoma Biol. Chem. 1990; Scholar) were not recognized by 2E1 or 3D11 The LpBs from both the HepG2 cells and the human cells for the of apoB MAbs and In an to the 2E1 and 3D11 we tested a of anti-apoB MAbs epitopes have been apoB structure X. Pease R. Bertinato J. Milne R.W. Well-defined regions of apolipoprotein B-100 undergo conformational change during its intravascular metabolism.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1301-1308Google Scholar) as as 2E1 and 3D11 for to with and for binding to immobilized human While of the MAbs could with or for binding to 2E1 and 3D11 did 2E1 and 3D11 to react with the or epitopes. tested the of 3D11 and between residues and for with a of apoB M.F. Taylor Young S.G. B.J. of forms of human apolipoprotein B in rat hepatoma cells. Evidence that the of apolipoprotein B has a on the density of the secreted Biol. Chem. Scholar) that had been separated by are for 2E1 and Both MAbs react with and weakly with Therefore, the epitopes are the 689 residues of of HuBTg+/+ mice with human LDL an immune response that was but specific for epitopes that the LDL for immunization from the of the human apoB was in the of hybridomas from the mice and in the of the MAbs that as we had we two MAbs and that between LpB synthesized in humans and in mice. In was specific for a of LDL isolated from human plasma. In the of an immune response against the of apoB of as can Two of the MAbs were specific for epitopes of human apoB that are expressed apoB conformation is modified by of lipoproteins to or a was the for of epitopes expressed on a of apoB can in the of the HuBTg+/+ of the HuBTg+/+ mice were immunized with LDL from FDB MAbs were that could between apoB-100 and the possibility that MAbs 2E1 and 3D11 detect polymorphisms in that is not the Plasma from all individuals tested to with human LDL for binding to 2E1 and 3D11 in a solid-phase Therefore, 2E1 and 3D11 were a function of apoB gene the by the human apoB in the normal LpB from HuBTg+/+ lipoproteins secreted by human apoB-100-transfected rat hepatoma cells did not react with 2E1 and 3D11 in a The apoB-100 to the cells B.J. An expression for human apolipoprotein B100 in a rat hepatoma Biol. Chem. 1990; Scholar) and the to the HuBTg+/+ mice (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar) were isolated from different is that the human apoB that is secreted in the two the apoB LDL from HuBTg+/+ transgenic mice are enriched in (7Linton M.F. Farese R.V. Chiesa G. Grass D.S. Chin P. Hammer R.E. Hobbs H.H. Young S.G. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037Google Scholar), is that for lack of 2E1 and 3D11 The of the human CETP gene or the human hepatic lipase gene the HuBTg+/+ mice did not to the expression of the 2E1 or 3D11 epitopes on the LpB. the cholesteryl LDLs from mice were not recognized by 2E1 and The 2E1 and 3D11 of the secreted by HepG2 cells that is not solely for the lack of expression of the epitopes on LpB of HuBTg+/+ mice. In the similar of human and LDL that the expression of the 2E1 and 3D11 epitopes is of both LpB and core lipid composition. the 2E1 and 3D11 epitopes were detected on LpB secreted by human HepG2 hepatoma cells but not on LpB secreted by human apoB-100-transfected rat hepatoma cells, the not from differences in the intravascular metabolism of LpB. we that posttranslational modification of apoB in rodent and human cells and that the expression of the 2E1 and 3D11 epitopes. Human apoB undergoes Lee B.R. and characterization of and of human apolipoprotein 1990; Scholar), N. The composition and of the of human low density Scholar), M. of low density of small apolipoprotein B.J. Biol. Chem. Scholar), and lipid modification D.M. of in apolipoprotein Biol. Scholar) the The 2E1 and 3D11 MAbs be specific for a modified or posttranslational modification of apoB could epitopes in native LpB of apoB transgenic mice. the 689 of apoB that the 2E1 and 3D11 is a site of S. Pownall H.J. Liu Li L. of apoB-100 of human low density Scholar) and residues that undergo Y. J. of apolipoprotein B is for and of and Biol. 2000; Scholar). is that a more of in human apoB expressed by rodent cells the 2E1 and 3D11 epitopes as of the site in by did not the 2E1 and 3D11 tested by a and The in the of native and apoB-100 that the epitope expression is not to differences in The of antibody that we with immunized transgenic mice as a of spleen cells to hybridomas the of immunization of transgenic mice the of the immune response to in the to conformational differences between the and the of and to in the that could be to MAbs against for transgenic mouse lines An example in the of lipoproteins be MAbs specific for Two of the MAbs we generated with protocol to differences between human apoB secreted by human cells and human apoB secreted by rodent cells. are for differences as as the The for technical and for an rat hepatoma cells were a from and was by from the of a from the and of cholesteryl ester transfer protein familial defective apoB apoB-containing lipoproteins monoclonal antibody McArdle 7777 rat hepatoma triglyceride

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