HEAVY-CHAIN ISOTYPE PATTERNS OF HUMAN ANTIBODY-SECRETING CELLS INDUCED BY HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN RELATION TO AGE AND PREIMMUNITY
T. Barington et al., HEAVY-CHAIN ISOTYPE PATTERNS OF HUMAN ANTIBODY-SECRETING CELLS INDUCED BY HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN RELATION TO AGE AND PREIMMUNITY, Infection and immunity, 62(8), 1994, pp. 3066-3074
The influence of preexisting immunity on the heavy-chain isotypes of c
irculating antibody-secreting cells (AbSC) induced by vaccination with
Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) c
oupled to tetanus toroid (TT) or diphtheria toroid (DT) and by vaccina
tion with TT or DT alone in 51 healthy adults and 9 infants was studie
d. In adults, the isotypes of TT and DT AbSC were dominated by immunog
lobulin G1 (IgG1) followed by IgG4 and IgA1. HibCP AbSC were dominated
by the isotype IgA1 followed by (in decreasing order) IgG2, IgA2, IgM
, and IgG1. The isotype distributions of TT and DT AbSC were independe
nt of whether the toxoids were coupled to HibCP, and the isotypes of H
ibCP AbSC were not influenced by the nature of the carrier (TT or DT).
Furthermore, the isotype distributions were unaffected by recent immu
nization with components of the conjugates, although this reduced the
numbers of AbSC. The heavy-chain gene usage of HibCP AbSC in adults di
ffered clearly from that in infants, which was restricted largely to t
he genes mu, gamma 1, and alpha 1, all tying upstream in the heavy-cha
in constant-region gene lotus,,while the usage in adults also, to diff
erent extents, involved the downstream genes gamma 2 and alpha 2. The
ratio between the numbers of HibCP AbSC using heavy-chain genes from t
he downstream duplication unit (gamma 2, gamma 4, and alpha 2) and tho
se using genes from the upstream duplication unit (gamma 3, gamma 1, a
nd alpha 1) correlated with the preimmunization level of natural HibCP
antibodies (r = 0.59; P = 0.00002). A possible role of natural exposu
re for Hib or cross-reactive bacteria on the mucosal surfaces in the s
haping of the isotype response to HibCP conjugate vaccines is discusse
d.