HEAVY-CHAIN ISOTYPE PATTERNS OF HUMAN ANTIBODY-SECRETING CELLS INDUCED BY HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN RELATION TO AGE AND PREIMMUNITY

Citation
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
Citations number
47
Categorie Soggetti
Immunology,"Infectious Diseases
Journal title
ISSN journal
00199567
Volume
62
Issue
8
Year of publication
1994
Pages
3066 - 3074
Database
ISI
SICI code
0019-9567(1994)62:8<3066:HIPOHA>2.0.ZU;2-6
Abstract
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.