NEONATAL MURINE B-LYMPHOCYTES RESPOND TO POLYSACCHARIDE ANTIGENS IN THE PRESENCE OF IL-1 AND IL-6

Unlike adults, neonates are unable to respond to polysaccharide Ags,ma king them especially vulnerable to pathogenic encapsulated bacteria. S ince the Ab response to polysaccharides in adult mice requires certain cytokines, it was hypothesized that neonatal murine B cells may be co mpetent to respond to such Ags, but may fail to do so due to a deficie ncy of cytokines. Neonatal splenocyte cultures, which were otherwise u nresponsive to trinitrophenyl (TNP)-Ficoll, a haptenated polysaccharid e Ag, mounted an adultlike Ab response when supplemented with IL-1. Ho wever, IL-1 failed to induce such a response to TNP-Ficoll when purifi ed B cells were used instead. Although IL-6 alone did not induce a res ponse in whole spleen cells or purified B cells from neonates, it syne rgized with IL-1 in inducing purified neonatal B cells to respond to T NP-Ficoll. The avidity of the cytokine-induced neonatal anti-TNP Abs w as comparable to that of Abs made by adult splenocyte cultures. One ef fect of IL-1 may be at the level of clonal expansion, since it induced neonatal B cells to proliferate in response to anti-IgM, which was fu rther enhanced by IL-6. The spontaneous secretion of IL-1 by neonatal splenocytes was below the detection limit, while adult splenocytes sec reted 30.8 +/- 5.2 U/ml, which is of the same order of magnitude as wh at was required to stimulate neonatal B cells to respond to TNP-Ficoll . Thus, the neonatal unresponsiveness to polysaccharide Ags could be d ue to the inability of a non-B cell population resident in the neonata l spleen to secrete sufficient quantities of IL-1.