Deliberate removal of T cell help improves virus-neutralizing antibody production.
The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4(+) T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4(+) T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8(+) T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.
Recher
Mike
M
Institute for Experimental Immunology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland. mike.recher@usz.ch
Lang
Karl S
KS
Hunziker
Lukas
L
Freigang
Stefan
S
Eschli
Bruno
B
Harris
Nicola L
NL
Navarini
Alexander
A
Senn
Beatrice M
BM
Fink
Katja
K
Lötscher
Marius
M
Hangartner
Lars
L
Zellweger
Raphaël
R
Hersberger
Martin
M
Theocharides
Alexandre
A
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001117:Arenaviridae Infections / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice