CpG dinucleotides overcome unresponsiveness of murine neonatal B cells to thymus independent type 2 antigens

Thymus Independent Type 2 (TI-2) antigens, elicit an immune response in adults but not in neonates, making neonates vulnerable to pathogenic bacteria that express TI-2 antigens. As such, immature neonatal B cells, unlike mature adult B cells, undergo growth arrest and apoptosis when stimulated with anti-IgM, a model TI-2 antigen. Previously, it had been shown that bacterial DNA or oligonucleotides (ODN) containing unmethylated CpG dinucleotides activate mature adult murine B cells to proliferate and differentiate into IgM secreting cells (Krieg et al. (1995) Nature 374:546). We found that CpG ODN enhanced proliferation of BKS-2, an immature B cell lymphoma, and protected it from anti-IgM induced apoptosis. Here we investigated the ability of CpG ODN to activate neonatal B cells. We show ODN containing the CpG motif stimulated purified neonatal B cells to proliferate implying that CpG directly acts on neonatal B cells. The CpG ODN also overcame the anti-IgM induced growth arrest in neonatal B cells. Further, CpG ODN and anti-IgM synergized in stimulating neonatal B cell proliferation. This ability of CpG to rescue neonatal B cells from anti-IgM induced growth arrest was also evident if the addition of CpG to cultures of neonatal B cells with anti-IgM was delayed for up to 18 hours. Both, the ability to induce proliferation or rescue neonatal B cells from anti-IgM induced apoptosis were not seen with ODN that did not contain the CpG motif. In conclusion, this could provide a novel approach to enhance the immune response in neonates.