Decreased expression of the ligand for CD40 in newborn lymphocytes.
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.
Fuleihan
R
R
Division of Immunology, Children's Hospital, Boston, MA 02115.
Ahern
D
D
Geha
R S
RS
D015152:Blotting, Northern; D023201:CD40 Ligand; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007231:Infant, Newborn / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate