Anti-CD23 monoclonal antibodies: comparisons of epitope specificities and modulating capacities for IgE binding and production.
A large battery of anti-CD23 mAb were compared for their epitope specificities and for their abilities to alter both IgE binding to cell-associated CD23 and IgE production in vitro in response to three sets of stimulants. The nine mAb tested can be divided into four families which define four antigenic epitopes (A-D) of CD23. Of these four families, two bind antigenic sites, (A and D) that appear to lie outside the IgE ligand binding site and two bind sites (B and C) that appear to be located within or close to this site, as determined by the abilities of appropriate mAb to alter IgE binding to CD23. The effects that these mAb had on IgE secretion by normal peripheral blood mononuclear cells (PBMNC) varied depending on the stimulant employed to induce IgE production. Interactions with epitope A, which was found to lie outside the ligand binding site and to be made more accessible by binding of mAb to other epitopes, had different effects on IgE production than interactions with the other epitopes. Indeed, mAb binding to this epitope lead to as much as a 10 fold enhancement in IgE biosynthesis induced by IL-4 alone or by IL-4 + hydrocortisone whereas interactions at the other sites resulted in almost complete inhibition of IgE production. In addition, mAb reactive with epitopes B and C had minimal effects on IgE production induced by IL-4 + anti-CD40 mAb whereas interactions at epitope A consistently enhanced IgE production. Finally, no apparent direct correlation was found between the ability of individual anti-CD23 mAb to alter IgE binding to cell-associated CD23 and their ability to modulate IgE production by PBMNC. These studies suggest that IgE binding to cell-associated CD23 does not have a major role in the de novo synthesis of IgE that involves CD23 interactions. In addition, the different effects that binding to epitope A vs B or C have on IgE synthesis suggest that molecular interactions between distinct portions of the CD23 molecule and other cell surface molecules expressed on the same B cell or adjacent communicating cells may lead to divergent cellular effects on IgE production. Finally these studies imply that only epitope A is involved in the generation of an IgE response through the CD40 pathway.
Wakai
M
M
Department of Medicine, North Shore University Hospital, Manhasset, NY 11030.
Pasley
P
P
Sthoeger
Z M
ZM
Posnett
D N
DN
Brooks
R
R
Hashimoto
S
S
Chiorazzi
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D019013:CD40 Antigens; D000939:Epitopes / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D000939:Epitopes; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E; D006854:Hydrocortisone