CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection.
It is generally believed that the production of influenza-specific IgG in response to viral infection is dependent on CD4 T cells. However, we previously observed that CD40-deficient mice generate influenza-specific IgG during a primary infection, suggesting that influenza infection may elicit IgG responses independently of CD4 T cell help. In the present study, we tested this hypothesis and show that mice lacking CD40 or CD4 T cells produce detectable titers of influenza-specific IgG and recover from influenza infection in a manner similar to that of normal mice. In contrast, mice completely lacking B cells succumb to influenza infection, despite the presence of large numbers of functional influenza-specific CD8 effector cells in the lungs. Consistent with the characteristics of a T-independent Ab response, long-lived influenza-specific plasma cells are not found in the bone marrow of CD40-/- and class II-/- mice, and influenza-specific IgG titers wane within 60 days postinfection. However, despite the short-lived IgG response, CD40-/- and class II-/- mice are completely protected from challenge infection with the same virus administered within 30 days. This protection is mediated primarily by B cells and Ab, as influenza-immune CD40-/- and class II-/- mice were still resistant to challenge infection when T cells were depleted. These data demonstrate that T cell-independent influenza-specific Ab promotes the resolution of primary influenza infection and helps to prevent reinfection.
Lee
Byung O
BO
Trudeau Institute, Saranac Lake, NY 12983, USA.
Rangel-Moreno
Javier
J
Moyron-Quiroz
Juan E
JE
Hartson
Louise
L
Makris
Melissa
M
Sprague
Frank
F
Lund
Frances E
FE
Randall
Troy D
TD
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000502:physiology; D019676:Genes, T-Cell Receptor delta / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007113:Immunity, Innate; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood; D007251:Influenza, Human / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012008:Recurrence
D000914:Antibodies, Viral; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G