Cross-linking of CD23 antigen by its natural ligand (IgE) or by anti-CD23 antibody prevents B lymphocyte proliferation and differentiation.
The possible role of CD23 in the activation of human B lymphocytes was systematically investigated by examining the effect of: 1) anti-CD23 mAb; 2) IgE or IgE-immune complexes and; 3) native or recombinant soluble CD23 of different m.w., on B cell proliferation. Intact anti-CD23 mAb or its F(ab')2 fragments inhibit the proliferation of tonsillar B lymphocytes costimulated with either Staphylococcus aureus Cowan I (SAC) or anti-IgM and IL-4. The antibody has no effect when IL-2 or LMW-BCGF is used as the second stimulant. The response of IL-4-pretreated B cells (expressing high levels of CD23) to anti-IgM together with IL-2 or B cell-derived B cell growth factor is inhibited by anti-CD23 mAb, indicating that this antibody prevents B cell activation regardless of the B cell activators but provided that the density of CD23 on B cells is sufficient. Anti-CD23 mAb markedly inhibits DNA synthesis only when added during the first 12 h of the culture and has no effect on the ongoing proliferation of CD23-bearing B cell blasts (SAC induced and IL-4 supported or EBV transformed). Monovalent Fab fragments of anti-CD23 mAb are inactive unless they are used in tandem with goat anti-mouse Fab suggesting that the inhibition is due to cross-linking of surface CD23. Most interestingly, polymeric IgE or IgE-immune complexes have the same effect as anti-CD23 and moreover they inhibit IgM production by SAC and IL4-stimulated B cells. The inhibiting effect of IgE or of anti-CD23 mAb is not due to their neutralization of soluble CD23 because these failed to display B cell growth factor activity under various experimental conditions. It is concluded that IgE-immune complexes may regulate activation and differentiation of CD23-bearing surfaceIgM/surfaceIgD precursor B lymphocytes.
Luo
H Y
HY
University of Montreal, Notre-Dame Hospital, Research Center, Canada.
Hofstetter
H
H
Banchereau
J
J
Delespesse
G
G
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D012995:Solubility
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E