Are cord blood B cells functionally mature?

Abstract

Very low immunoglobulin secretion occurs in pokeweed mitogen (PWM) stimulated cord blood mononuclear cells (MNC) and has been attributed to an 'immaturity' of both T and B cells of the newborn. The cord blood T cells are phenotypically 'naive' cells, in which suppressor activity for B cell function appears to dominate over helper activity. The cord blood B cells, in spite of their expression of different membrane immunoglobulin isotypes, secrete almost no IgG and IgA in the various B cell assays so far compared. We found that cord blood B cells are as competent as B cells from adults to generate clonal IgM, IgG and IgA responses in a culture system in which a cell contact with mutant EL-4 thymoma cells in conjunction with T cell supernatant leads to strong B cell activity. As regarding the possible causes of the low cord blood PWM response, we studied the role of transforming growth factor-beta 1 (TGF-beta 1), a potent inhibitor of lymphocyte functions. TGF-beta 1 sensitivity of B cells and TGF-beta 1 mRNA levels in MNC were found to be similar for adult and cord blood cells. A neutralizing anti-TGF-beta 1 antibody enhance the adult PWM response, but the immunoglobulin secretion in cord MNC remained very low. We conclude that suppression by endogenous TGF-beta 1 occurs in the PWM system but is not responsible for the low immunoglobulin response of cord blood MNC and that the newborn's B cell 'immaturity' can be overcome with potent T cell signals in vitro. This is consistent with the newborn's capacity to generate a T-dependent B cell response in vivo.