Heterogeneity of degradation of B-cell endocytosed monoclonal antibodies reacting with different sIgM epitopes.
The degradation of a panel of monoclonal antibodies (MoAb) bound to surface IgM (sIgM) was studied in three human Burkitt's lymphoma cell lines. The panel included MoAb that recognize several distinct epitopes associated with the F(c mu)5 domain, the c mu 2 domain and kappa or lambda light chains. The amount of degraded MoAb and the rate of their degradation varied considerably between the various antibodies. Properties of MoAb such as avidity or ability to cross-link sIgM did not significantly influence their degradation. The most consistent correlation between rate of degradation and MoAb used was the location of the epitope recognized by the individual MoAb. Thus, 7 out of 8 anti-light chain MoAb were degraded at a higher rate than 5 out of 5 anti-F(c mu)5 MoAb. One anti-c mu 2 MoAb was degraded at a rate similar to the majority of anti-light chain MoAb. The intracellular transport of an anti-kappa light chain MoAb and an anti-F(c mu)5 MoAb was studied in detail by subcellular fractionation in sucrose gradients. We found that the anti-kappa light chain MoAb was transported more rapidly to lysosomes than the anti-F(c mu)5 MoAb, showing that they were sorted differently intracellularly.
Ruud
E
E
Department of Pathology, Norwegian Radium Hospital, Oslo.
Michaelsen
T
T
Kindberg
G M
GM
Berg
T
T
Funderud
S
S
Godal
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D001667:Binding, Competitive; D002460:Cell Line; D003429:Cross Reactions; D004705:Endocytosis; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D012995:Solubility; D013347:Subcellular Fractions / Q000032:analysis; D014238:Trichloroacetic Acid
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011947:Receptors, Antigen, B-Cell; D014238:Trichloroacetic Acid