Occupancy of CD72 (the CD5 counterstructure) enhances interleukin-4-dependent CD23 expression in resting B lymphocytes.

CD72, the human homologue of murine Lyb-2, was recently identified as a counterstructure to CD5. An antibody to CD72 (BU40) has been found to mimic interleukin-4 (IL-4) both in its ability to activate resting B cells into the early G1 phase of cell cycle and to augment the expression of major histocompatibility complex (MHC) class II antigen; unlike IL-4, the CD72-clustered antibody fails to induce the expression of CD23. We now report that engagement of CD72 by the IgG monoclonal antibody BU40 potentiates the capacity of IL-4--when used at optimal concentrations--to promote CD23 production in human B cells. The degree of enhancement arising from occupancy of CD72 ranged from two- to fivefold. Importantly, antibody to CD72 was also found to diminish the concentration required for IL-4 to promote CD23 expression to a level equivalent to that maximally achieved when using IL-4 alone. Engagement of CD72 by BU40 not only increased the amount of cell-associated CD23 induced by IL-4 but also led to augmented release of soluble material into the culture medium. Monovalent Fab fragments of BU40 antibody were as efficient as intact antibodies at synergizing with IL-4 for enhanced expression and release of CD23: thus simple tethering without the need for receptor cross-linking was sufficient to invoke change through CD72. Enhancement of CD23 expression via CD72 appeared to be selective for IL-4-dependent induction: the turn on of CD23 by tumour-promoting phorbol ester was left unaltered on the addition of BU40 antibody. Engagement of CD72 had no effect on the IL-4-promoted hyperexpression of surface IgM. The findings are discussed within the context of the molecular and functional interactions occurring during T-B collaboration.