Coordinated action of IgE and a B-cell-stimulatory factor on the CD23 receptor molecule up-regulates B-lymphocyte growth.

Abstract

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 =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.

Regulation of the Expression of the Low-Affinity IgE Receptor (FcεRII) in the Human Monocyte-Like Cell Line U-937 by Phorbol Esters and IgE

“…It is, therefore, possi ble that IgE acts through two different mechanisms: the one being cycloheximide sensitive, while the other, which can be uncovered by a longer exposure to IgE, is independent of protein synthesis and is probably based on the extension of FceRII half-life. Results similar to ours have been obtained with B lymphocytes [21,35]. Moreover, Delespesse et al [36] found evidence that IgE protects FceRII from prote olysis; they have also recently described a FceRI ¡-as sociated proteolytic activity [37].…”

“…We and others [16,17] have shown that phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), can upregulate the expression of FceRII in U-937 cells. It is also known that the expression of the low-affinity receptor for IgE can be stimulated by the ligand in a variety of systems, both in vivo and in vitro [18][19][20], Guy and Gordon [21] demonstrated that IgE increases by a fac tor of 5 the TPA-induced expression of FceRII on hu man B lymphocytes. This study is aimed at the investi gation of the combined effect of TPA and IgE on the expression of FceRII on U-937 cells and the possible mechanisms of upregulation.…”

Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes.

“…In contrast, it has been recently reported that IFN-y has a strong inhibitory effect on the IL-4-dependent induction of FceR2/CD23 on human B cells (20). In addition, phorbol esters could not increase FceR2/CD23 expression on Mo, while an inducing effect has been recently described for B cells (23,24) . Recent evidence suggests that FceR2/ CD23 may play a crucial role in growth signal transduction on the B cell surface (23)(24)(25)(26) .…”

Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells.

“…Another early effect of IL-4 on normal resting B cells is the upregulation of the expression of CD23 (16,25,26). We thus examined whether this effect could take place in B-CLL lymphocytes.…”