Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity. Infect. Immun

The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or DT alone in 51 healthy adults and 9 infants was studied. In adults, the isotypes of TT and DT AbSC were dominated by immunoglobulin Gl (IgGI) followed by IgG4 and IgAl. HibCP AbSC were dominated by the isotype IgAl followed by (in decreasing order) IgG2, IgA2, IgM, and IgGl. The isotype distributions of TT and DT AbSC were independent of whether the toxoids were coupled to HibCP, and the isotypes of HibCP AbSC were not influenced by the nature of the carrier (TT or DT). Furthermore, the isotype distributions were unaffected by recent immunization with components of the conjugates, although this reduced the numbers of AbSC. The heavy-chain gene usage of HibCP AbSC in adults differed clearly from that in infants, which was restricted largely to the genes FL, yl, and al, all lying upstream in the heavy-chain constant-region gene locus, while the usage in adults also, to different extents, involved the downstream genes y2 and a2. The ratio between the numbers of HibCP AbSC using heavy-chain genes from the downstream duplication unit (-y2, y4, and a2) and those using genes from the upstream duplication unit (y3,-yl, and al) correlated with the preimmunization level of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib o