Differential idiotype utilization for the in vivo type 14 capsular polysaccharide-specific Ig responses to intact Streptococcus pneumoniae versus a pneumococcal conjugate vaccine.
Murine IgG responses specific for the capsular polysaccharide (pneumococcal capsular polysaccharide serotype 14; PPS14) of Streptococcus pneumoniae type 14 (Pn14), induced in response to intact Pn14 or a PPS14-protein conjugate, are both dependent on CD4(+) T cell help but appear to use marginal zone versus follicular B cells, respectively. In this study, we identify an idiotype (44.1-Id) that dominates the PPS14-specific IgG, but not IgM, responses to intact Pn14, isolated PPS14, and Group B Streptococcus (strain COH1-11) expressing capsular polysaccharide structurally identical to PPS14. The 44.1-Id, however, is not expressed in the repertoire of natural PPS14-specific Abs. In distinct contrast, PPS14-specific IgG responses to a soluble PPS14-protein conjugate exhibit minimal usage of the 44.1-Id, although significant 44.1-Id expression is elicited in response to conjugate attached to particles. The 44.1-Id elicited in response to intact Pn14 was expressed in similar proportions among all four IgG subclasses during both the primary and secondary responses. The 44.1-Id usage was linked to the Igh(a), but not Igh(b), allotype and was associated with induction of relatively high total PPS14-specific IgG responses. In contrast to PPS14-protein conjugate, avidity maturation of the 44.1-Id-dominant PPS14-specific IgG responses was limited, even during the highly boosted T cell-dependent PPS14-specific secondary responses to COH1-11. These results indicate that different antigenic forms of the same capsular polysaccharide can recruit distinct B cell clones expressing characteristic idiotypes under genetic control and suggest that the 44.1-Id is derived from marginal zone B cells.
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Jesus
J
Colino
Leah
L
Duke
Swadhinya
S
Arjunaraja
Quanyi
Q
Chen
Leyu
L
Liu
Alexander H
AH
Lucas
Clifford M
CM
Snapper
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D016667:Bacterial Capsules / Q000008:administration & dosage / Q000276:immunology*; D001666:Binding Sites, Antibody; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007130:Immunoglobulin Idiotypes; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C056696:pneumococcal polysaccharide, type 14