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.
Institute for Experimental Immunology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland. mike.recher@usz.ch
Mike
M
Recher
Karl S
KS
Lang
Lukas
L
Hunziker
Stefan
S
Freigang
Bruno
B
Eschli
Nicola L
NL
Harris
Alexander
A
Navarini
Beatrice M
BM
Senn
Katja
K
Fink
Marius
M
Lötscher
Lars
L
Hangartner
Raphaël
R
Zellweger
Martin
M
Hersberger
Alexandre
A
Theocharides
Hans
H
Hengartner
Rolf M
RM
Zinkernagel
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