Enhancement of antigen-specific immunoglobulin G responses by anti-CD48

CD48 is a glycosylphosphatidylinositol-anchored protein expressed ubiquitously on many cell types. Despite the poor ability to signal on its own, CD48 can activate cells via interaction with its counter receptors CD2 and CD244 as well as influence the function of other cell surface molecules by costimulatory activities. We show, herein, that injection of anti-CD48 antibodies into mice can augment the antibody response to a T-independent antigen, NP-Ficoll, that is representative of antigenic determinants expressed on the surface of various pathogens, such as Streptococcus pneumoniae. In C57BL/6 mice, enhancement of the response is dependent on natural killer (NK) cells as well as on the presence of CD2 and CD244, ligands for CD48, suggesting a requirement for direct interaction between NK and B cells. Interestingly, in this case, despite a similar augmentation by anti-CD48 in BALB/C mice, the response is independent of NK or T cells, suggesting that help for this response can be derived from other innate cell types. These results provide a pathway by which CD48, when appropriately activated, can influence the course of an antigen-specific antibody response via the innate system.