In vivo antibody synthesis against thymus-independent type 2 (TI-2) antigens such as type-specific polysaccharides of pneumococci is low or absent during the first 2 years of life. Recently, we described a role for CR2 in the in vitro antibody response of B cells of adults to the TI-2 antigen type 4 pneumococcal polysaccharide. In the present study a decreased expression of CR2 is described on cord blood B cells using HB5 and OKB7 anti-CR2 MAb. Crosslinking of HB5 anti-CR2 antibodies on the B cell membrane leads to increases in intracellular calcium ([Ca2+]i) in both adult and neonatal B cells. In adult B cells, a synergism between CR2 and sIgM could be demonstrated on the level of calcium mobilization by occupying CR2 and crosslinking of sIgM with substimulatory concentrations of anti-IgM antibodies. This synergistic action between CR2 and sIgM could not be demonstrated in neonatal B cells. In addition, it is demonstrated that HB5 MAb cannot induce B cell differentiation in neonatal B cells, while adult B cells can be induced to differentiate into Ig-producing cells by this MAb.