Coordinated action of IgE and a B-cell-stimulatory factor on the CD23 receptor molecule up-regulates B-lymphocyte growth.
The CD23 (BLAST-2) antigen, recently identified as the low-affinity IgE receptor of B lymphocytes, has also been implicated as the focus for growth-promoting signals delivered to activated B cells by a low molecular weight B-cell growth factor (BCGF). Here we show that IgE and BCGF can coordinate B-lymphocyte growth through their opposing effects on the CD23 molecule. While the activation of purified quiescent B cells with phorbol 12-myristate 13-acetate led to the induction of 45-kDa CD23 at the surface membrane, the inclusion of IgE increased CD23 expression by a factor of approximately equal to 5. The addition of BCGF resulted in the rapid release of a 35-kDa form of CD23 from the cell surface. This shed molecule is associated with autocrine growth factor activity. Substantially more of this material was generated by BCGF acting on cells that had been stimulated in the presence of IgE. The combined effects of IgE and BCGF on DNA synthesis in activated B cells were more than additive. IgE similarly augmented the stimulatory capacity of a CD23 antibody that mimics the biological actions of BCGF. Binding of the anti-receptor antibody to its 45-kDa target at the B-cell surface also prompted the release of the 35-kDa soluble species. These results demonstrate a pleiotropy in the CD23 molecule with regard to both ligand binding and the subsequent behavior of the receptor. The ability of this single receptor to orchestrate a B-lymphocyte response through a variety of ligands and its role in normal and transformed autocrine growth are discussed.
D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D002460:Cell Line; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D011961:Receptors, Fc / Q000276:immunology; D017455:Receptors, IgE; D011971:Receptors, Immunologic / Q000276:immunology
D000906:Antibodies; D006133:Growth Substances; D008222:Lymphokines; D011961:Receptors, Fc; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D015847:Interleukin-4; D007073:Immunoglobulin E