In vitro induction of IgG1 and IgG2 secretion by B cells of children who developed invasive haemophilus disease despite vaccination

Abstract

Lymphocytes from seven patients who developed Haemophilus influenzae type b (Hib) disease after being vaccinated with Hib polysaccharide vaccine and from one patient who developed disease after conjugate vaccination were investigated for the ability to secrete IgG1 and IgG2, in vitro, in response to a combination of pokeweed and Staphylococcus aureus Cowan I mitogens. The eight patients were selected because they had low anticapsular antibody responses to Hib disease. Only one of the eight children had a history of previous severe, recurrent infections. This child (in whom a polysaccharide vaccine failed) had a deficiency of the second component of complement and also had a subnormal serum concentration of IgG4. Only one of the eight children, an otherwise healthy 54-mo-old with normal serum Ig concentrations, had subnormal mitogen-induced B-cell secretion of IgG1 and/or IgG2. When this child's lymphocytes were separated into T- and B-cell fractions and cocultivated with the respective fractions of the father's lymphocytes, the child appeared to have an intrinsic B-cell defect and normal T cells. There were no significant differences (p greater than 0.3) in the respective geometric means of the in vitro secretion of IgG1 or IgG2 of the B cells from the children with polysaccharide vaccine failure and those of 14 healthy controls of similar ages as the patients (IgG1, 1524 versus 3497 ng/mL per 10(5) lymphocytes; IgG2, 79 versus 89 ng/mL per 10(5) lymphocytes). Thus, despite the presence of impaired serum anticapsular antibody responses to Hib disease, most children who develop Hib disease after Hib polysaccharide vaccination have normal in vitro B-cell secretion of IgG1 and IgG2 in response to mitogens.