Decreased expression of the ligand for CD40 in newborn lymphocytes

Abstract

Immune responses in newborn lymphocytes show a defect in isotype switching from IgM to IgG and IgA. Immunoglobulin isotype switching in B lymphocytes requires a contact-dependent signal from T lymphocytes which is delivered by the ligand for the B cell surface antigen CD40. We investigated the capacity of newborn lymphocytes to express the CD40 ligand and to undergo CD40 ligand-dependent immunoglobulin isotype switching. After stimulation by phorbol ester and ionomycin, newborn lymphocytes expressed markedly decreased amounts of CD40 ligand on their surface compared to normal adult lymphocytes. Northern blot analysis of mRNA derived from activated cord blood lymphocytes also revealed markedly decreased amounts of CD40 ligand mRNA. Decreased expression of CD40 ligand in newborn lymphocytes was associated with a severely decreased ability to undergo T cell-dependent immunoglobulin isotype switching. Newborn lymphocytes synthesized little or no detectable IgE in response to T cell-dependent stimulation by interleukin-4 but synthesized IgE in response to T cell-independent stimulation by CD40 monoclonal antibody and interleukin-4. These results indicate that decreased expression of CD40 ligand in newborn lymphocytes may be the underlying cause of deficient immunoglobulin isotype switching in newborns.

Longitudinal Survey of Lymphocyte Subpopulations in the First Year of Life

“…It is generally regarded as an activation marker (28). However, we and others (1,27,29,30) did not find other markers of activation in neonatal cord or infant blood, such as increased expression of CD25, HLA-DR, CD69, and CD154 (CD40 ligand). Nor did we find an increase of thymocyte-like CD1a ϩ or CD4 ϩ /CD8 ϩ double-positive T cells.…”

Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens

“…Two potential molecules are CD40L and IFN␥. First, as CD40L is poorly expressed by activated neonatal CD4 ϩ T cells, 18,[56][57][58][59][60] we hypothesized that mature levels of CD40L on activated donor CD4 ϩ T cells were necessary for the development of neonatal antidonor T-cell responses. However, when neonates were exposed to CD40L Ϫ/Ϫ donor cells, they were able to develop vigorous antidonor CTL and Th1/Th2 responses ( Figure 7A and data not shown), demonstrating that donor CD40L is not necessary for the development of neonatal allospecific T-cell responses.…”

Expression of CD21 and CD23 during Human Fetal Development

“…In contrast, IL-4 production by umbilical cord blood mononuclear cells is consistently described as lower than that from adult peripheral blood mononuclear cells, irrespective of the stimulus used (14,20). The lack of IL-4 and/or CD40 ligand may be the limiting factor in IgE production by the neonate, as a number of investigators have found that exogenous IL-4 in conjunction with CD40 cross-linking increased IgE production by umbilical cord blood mononuclear cells (13,14,16,17).…”

“…Neonatal B-cell expression of CD40 is similar to the adult (12), and responses to CD40 stimulation can be induced (13,14). Expression of CD40 ligand (CD40L, CD154) is variably described as reduced or comparable to the adult, depending upon the stimulation used (12,13,(15)(16)(17)(18)(19).…”