Suppression of IgE responses in CD23-transgenic animals is due to expression of CD23 on nonlymphoid cells.

Serum IgE is suppressed in CD23-transgenic (Tg) mice where B cells and some T cells express high levels of CD23, suggesting that CD23 on B and T cells may cause this suppression. However, when Tg B lymphocytes were compared with controls in B cell proliferation and IgE synthesis assays, the two were indistinguishable. Similarly, studies of lymphokine production suggested that T cell function in the Tg animals was normal. However, adoptive transfer studies indicated that suppression was seen when normal lymphocytes were used to reconstitute Tg mice, whereas reconstitution of controls with Tg lymphocytes resulted in normal IgE responses, suggesting that critical CD23-bearing cells are irradiation-resistant, nonlymphoid cells. Follicular dendritic cells (FDC) are irradiation resistant, express surface CD23, and deliver iccosomal Ag to B cells, prompting us to reason that Tg FDC may be a critical cell. High levels of transgene expression were observed in germinal centers rich in FDC and B cells, and IgE production was inhibited when Tg FDCs were cultured with normal B cells. In short, suppressed IgE production in CD23-Tg mice appears to be associated with a population of radioresistant nonlymphoid cells. FDCs that interface with B cells in the germinal center are a candidate for explaining this CD23-mediated IgE suppression.

Follicular dendritic cells and the maintenance of IgE responses.

Antigen (Ag) is retained for long periods of time in secondary lymphoid tissues in the form of immune complexes on follicular dendritic cells (FDC). Ag retained on FDC is thought to play a role in maintaining antibody (Ab) responses in vivo. A model for study of Ab production induced by retained Ag in vitro is the spontaneous Ab response. In this response, specific Ab production is induced spontaneously (no exogenous Ag needed) in cultures derived from secondary lymphoid tissues containing persisting Ag. Specific IgG is spontaneously induced and we reasoned that FDC may also play a role in the maintenance of specific IgE responses. To test this hypothesis, we monitored spontaneous anti-ovalbmin (OVA) IgE production in cultures of lymph node (LN) fragments from OVA-immunized mice. In addition, highly enriched preparations of OVA bearing FDC were added to OVA-specific memory cells in an attempt to stimulate OVA-specific IgE production. Months after secondary immunization, anti-OVA IgE responses were spontaneously induced when fragments from draining LN were placed into culture. Furthermore, FDC bearing OVA from draining LN induced anti-OVA IgE production when incubated with spleen cells from OVA-immune mice whereas identical cultures with FDC bearing environmental Ag from non-draining LN of the OVA immune animals did not. The anti-OVA IgE responses were elicited only in cultures containing OVA-immune memory cells indicating that specific memory cells were critical for these anti-OVA IgE responses. Removal of FDC from cultures with an FDC-specific mAb dramatically decreased anti-OVA IgE production. These studies demonstrate that FDC can induce specific memory T and B cells to produce IgE and help support the concept that FDC-associated antigen may be involved in the long-term maintenance of specific IgE responses.