Activation of virus-specific memory B cells in the absence of T cell help.
Humoral immunity is maintained by long-lived plasma cells, constitutively secreting antibodies, and nonsecreting resting memory B cells that are rapidly reactivated upon antigen encounter. The activation requirements for resting memory B cells, particularly the role of T helper cells, are unclear. To analyze the activation of memory B cells, mice were immunized with human cytomegalovirus, a complex human herpesvirus, and tick-born encephalitis virus, and a simple flavivirus. B cell populations devoid of Ig-secreting plasma cells were adoptively transferred into T and B cell-deficient RAG-1-/- mice. Antigenic stimulation 4-6 d after transfer of B cells resulted in rapid IgG production. The response was long lasting and strictly antigen specific, excluding polyclonal B cell activation. CD4+ T cells were not involved since (a) further depletion of CD4+ T cells in the recipient mice did not alter the antibody response and (b) recipient mice contained no detectable CD4+ T cells 90 d posttransfer. Memory B cells could not be activated by a soluble viral protein without T cell help. Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response. Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.
Hebeis
Barbara J
BJ
Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.
Klenovsek
Karin
K
Rohwer
Peter
P
Ritter
Uwe
U
Schneider
Andrea
A
Mach
Michael
M
Winkler
Thomas H
TH
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004195:Disease Models, Animal; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018398:Homeodomain Proteins; C064658:RAG-1 protein