TY - JOUR
T1 - Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity
AU - Barington, T
AU - Juul, Lars
AU - Gyhrs, A
AU - Heilmann, C
PY - 1994
Y1 - 1994
N2 - 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 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 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 mu, gamma 1, and alpha 1, all lying upstream in the heavy-chain constant-region gene locus, while the usage in adults also, to different extents, involved the downstream genes gamma 2 and alpha 2. The ratio between the numbers of HibCP AbSC using heavy-chain genes from the downstream duplication unit (gamma 2, gamma 4, and alpha 2) and those using genes from the upstream duplication unit (gamma 3, gamma 1, and alpha 1) correlated with the preimmunization level of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed.
AB - 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 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 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 mu, gamma 1, and alpha 1, all lying upstream in the heavy-chain constant-region gene locus, while the usage in adults also, to different extents, involved the downstream genes gamma 2 and alpha 2. The ratio between the numbers of HibCP AbSC using heavy-chain genes from the downstream duplication unit (gamma 2, gamma 4, and alpha 2) and those using genes from the upstream duplication unit (gamma 3, gamma 1, and alpha 1) correlated with the preimmunization level of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed.
KW - Adult
KW - Age Factors
KW - Antibodies, Bacterial
KW - Antibody-Producing Cells
KW - Bacterial Capsules
KW - Female
KW - Haemophilus Vaccines
KW - Haemophilus influenzae
KW - Humans
KW - Immunoglobulin Heavy Chains
KW - Immunoglobulin Isotypes
KW - Infant
KW - Male
KW - Polysaccharides, Bacterial
KW - Vaccination
M3 - Journal article
C2 - 8039873
SN - 0019-9567
VL - 62
SP - 3066
EP - 3074
JO - Infection and Immunity
JF - Infection and Immunity
IS - 8
ER -