NEGATIVE FEEDBACK-REGULATION OF IGE SYNTHESIS BY MURINE CD23

IMMUNOGLOBULIN E is found in nanogram amounts in normal human and mous e serum. It is increased during parasitic infestations(1) and mediates allergy. CD23, the low-affinity receptor for IgE (Fc epsilon RII), ha s been proposed as an important regulator of IgE synthesis(2-4). The t ype-II transmembrane lectin(4) CD23 is expressed in the mouse on B cel ls and follicular dendritic cells. In humans there are two forms of CD 23 which differ in their intracellular amino-terminal 6/7 amino acids( 4); expression of the A-form corresponds to that of murine CD23, where as the B-form is also found on T and other haematopoietic cells(4). CD 23 has been implicated in cellular adhesion(5), antigen presentation(6 ), as a growth and differentiation factor for human B, T and plasma ce lls, and as a signal transduction molecule(7) (reviewed in refs 3, 8). Here we disrupt the gene coding for murine CD23 (ref. 9) to clarify t he role of CD23 in vivo and find that B- and T-cell development is nor mal in these CD23-deficient mice. Immune responses to the helminth Nip postrongylus brasiliensis are unaffected, In contrast, immunization wi th thymus-dependent antigens leads to increased and sustained specific IgE antibody titres compared with controls. Formation of germinal cen tres is normal. These results suggest that murine CD23 acts as a negat ive feedback component of IgE regulation.