Triggering of B lymphocytes through CD23: epitope mapping and studies using antibody derivatives indicate an allosteric mechanism of signalling.
By using five monoclonal antibodies in reciprocal cross-locking studies, a minimum of three epitope clusters have been defined for the B-cell restricted, activation-associated CD23 antigen. Two of the five antibodies were capable of replacing low molecular weight B-cell growth factor (BCGF) in B-cell co-stimulation assays. These two antibodies belonged to the same epitope group, while non-stimulatory antibodies fell outside this cluster. By prior coating of activated B lymphocytes at 4 degrees, all five CD23 antibodies interfered with the subsequent uptake of BCGF activity onto the cells. However, only the two stimulatory antibodies were capable of inhibiting the absorption of BCGF completely. From one of these antibodies, F(ab')2 and Fab fragments were generated and both were found to be equivalent to whole antibody in their ability to mimic BCGF. Immobilized antibody, however, failed to stimulate over a wide range of concentrations. These findings demonstrate that the ability of certain CD23 antibodies to deliver a growth-promoting signal to activated B cells is independent not only of the Fc portion of the molecule but also of receptor cross-linking. The latter observation is indicative of an allosteric mechanism of triggering, a notion supported by the epitope specificity of activation through CD23. The findings are discussed in relation to the putative natural ligands for CD23 and the way they may influence B-cell function through this receptor.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive; D000939:Epitopes / Q000032:analysis*; D006133:Growth Substances / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D000939:Epitopes; D006133:Growth Substances; D007140:Immunoglobulin Fab Fragments; D008222:Lymphokines; D015847:Interleukin-4