CD4 T Cell-Independent Antibody Response Promotes Resolution of Primary Influenza Infection and Helps to Prevent Reinfection

Abstract

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.

SAP Is Required for Th Cell Function and for Immunity to Influenza

“…One report found increased mortality of SAP KO mice during chronic LCMV infection (8), but whether this was related to the Ab defect was not investigated. Our data show that SAP is not required for control of primary influenza infection, which is consistent with another report showing that mice deficient in T cell help due to CD40 deficiency or MHC class II deficiency control primary influenza infection as WT mice do (32). Despite control of primary infection, our data demonstrate that SAP is required for preventing secondary high dose influenza infection, and that IgG in serum from WT, but not SAP KO mice can protect mice against lethal infection.…”

B Cells Promote Resistance to Heterosubtypic Strains of Influenza via Multiple Mechanisms

“…In addition, the virulence of the challenge virus is important. For example, even naive MT mice can clear the relatively avirulent X31 virus, but they rarely survive infection with the virulent PR8 virus (37). Thus, the importance of B cells in resistance to heterosubtypic infections is magnified by the dose and virulence of the challenge virus.…”

TLR Signaling Fine-Tunes Anti-Influenza B Cell Responses without Regulating Effector T Cell Responses

“…Protective immunity against a primary infection with lethal type A influenza virus is to a large degree mediated by the humoral response, as shown by studies in which mice lacking B cells rapidly succumb to influenza infection despite the ability to mount a vigorous CD8 ϩ T cell response (1,2). Class switch recombination to Ab isotypes other than IgM is largely dependent upon T cell help, although Abs of the IgG isotypes are detectable at reduced titers in the absence of T-B interaction (3)(4)(5). Detailed analysis of the efficacy of Ab isotypes showed that IgG isotypes are primarily responsible for neutralizing influenza virus during primary and challenge infections (6,7), and earlier studies identified IgG2a as a key isotype for Ab-mediated effector functions in C57BL/6 mice (8 -10).…”