The capsular polysaccharides of some bacteria, including Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis, are T cell-independent antigens (TI). They induce only weak antibody responses, predominantly with immunoglobulin M (IgM), and infants respond particularly poorly. However, if T-cell help is given to B cells during responses to these antigens, stronger antibody responses and isotype switching to IgG can be induced. CD40 ligand on T cells interacts with CD40 on B cells, resulting in activation of B cells; thus, anti-CD40 antibodies capable of activating B cells can substitute for T-cell help. Dullforce et al., 1998 Dullforce P. et al. Enhancement of T cell-independent immune responses in vivo by CD40 antibodies. Nat. Med. 1998; 4: 88-91 Crossref PubMed Scopus (95) Google Scholar report that when type 3 pneumococcal capsular polysaccharide (PS3), together with an anti-CD40 monoclonal antibody (CD40-mAb), capable of activating B cells, was administered to mice, long-lasting IgG responses against PS3 were seen, and memory B cells specific for PS3 were detected. Sixty percent of mice immunized with PS3 and CD40-mAb survived after challenge by S. pneumoniae, but none of the mice immunized with PS3 alone survived. CBA/N (xid) mice have an X-linked immunodeficiency in which immature B cells producing IgM are predominantly seen. Thus, like infants, they are unable to respond to TI type II antigens. In such mice, this immunization regime generates IgG antibody responses against PS3, and the B-cell defect is successfully bypassed by the CD40-mAb. Thus, the CD40-mAb may be able to work as an adjuvant for T cell-independent antigens, especially in infants with immature B cells or in AIDS patients lacking effective T-cell help.