MODULATION OF THE LOW-AFFINITY IGE FC RECEPTOR (FC-EPSILON-RII CD23) BY LEISHMANIA-CHAGASI

Mature B lymphocytes and macrophages express low-affinity receptors for IgE (CD23 or FcepsilonRII), a multifunctional molecule involved in IgE regulation, B cell growth and antigen presentation. We studied the effect of the protozoan Leishmania chagasi on CD23 expression using a model of early disease. Murine and human B cells, B cell lines, and a macrophage cell line incubated in vitro with the promastigote (PM) form of L. chagasi showed a selective loss of CD23 expression as detected by mAbs and IgE binding. Other B cell surface markers (class II MHC, CD32, surface IgM, surface IgD and gp90MEL-14) remained unchanged, indicating the loss was not due to B cell activation. The CD23 loss was parasite dose-dependent and required contact between PM and B cells. There was a loss of splenic B cell CD23 expression 24 h after infection of BALB/c mice with PM, indicating that the effect also occurred in vivo. During the activation of normal B cells, CD23 is cleaved by a cell-associated protease and released as a soluble form (sCD23). The human B cell line RPMI 8866 showed a 3- to 10-fold increase in the amount of sCD23 released into cultured supernatants when incubated with L. chagasi PM, which paralleled the loss of membrane-bound CD23 from the cell surface. In contrast, the steady-state level of CD23 mRNA did not change appreciably in RPMI 8866 cells during co-culture with PM. Thus, L. chagasi PM selectively down-modulated CD23 expression on B cells and macrophage cell lines, at least in part by increasing the release of sCD23.