Delayed IgG2 humoral response in infants is not due to intrinsic T or B cell defects.
The physiologically low or absent IgG2 responses of infants have been attributed to T or B cell functional immaturity. We have analyzed the capacity of adult and neonatal T lymphocytes to secrete IgG2 switch factor (IgG2-SF) and the capacity of neonatal B cells to respond to such factors. The IgG2-SF capacity was assessed on CD40-activated naive B cells, measuring IgG2 by ELISA in supernatants of cultures performed in the presence of IL-10. T cells secreted IgG2-SF together with IL-2 and IFN-gamma, after activation with a combination of anti-CD2, anti-CD28 and phorbol myristate acetate (Th1-like activation). In contrast, activation with anti-CD3 and anti-CD28, which yielded IL-4 and IL-10 but neither IL-2 nor IFN-gamma (Th2-like activation), did not result in the secretion of IgG2-SF. The supernatant of activated neonatal T cells contained IgG2-SF. Neonates' B cells produced almost as much IgG2 as did naive adult B cells. The effect of IgG2-SF was further demonstrated by its ability to induce 3-15% of CD40-activated naive B cells to express cytoplasmic IgG2 regardless of the presence of IL-10. This study demonstrates that: (i) IgG2 switch can be T cell dependent in humans, (ii) IgG2-SF is produced with Th1-like cytokines and (iii) low IgG2 responses in infants do not result from either an inability of T cells to produce IgG2-SF or an inability of B cells to undergo IgG2 switch in vitro.
Servet-Delprat
C
C
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Bridon
J M
JM
Djossou
O
O
Yahia
S A
SA
Banchereau
J
J
Brière
F
F
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D007074:Immunoglobulin G