Type I IFN enhances follicular B cell contribution to the T cell–independent antibody response

Abstract

Humoral immunity to viruses and encapsulated bacteria is comprised of T cell–independent type 2 (TI-2) antibody responses that are characterized by rapid antibody production by marginal zone and B1 B cells. We demonstrate that toll-like receptor (TLR) ligands influence the TI-2 antibody response not only by enhancing the overall magnitude but also by skewing this response to one that is dominated by IgG isotypes. Importantly, TLR ligands facilitate this response by inducing type I interferon (IFN), which in turn elicits rapid and significant amounts of antigen-specific IgG2c predominantly from FO (follicular) B cells. Furthermore, we show that although the IgG2c antibody response requires B cell–autonomous IFN-α receptor signaling, it is independent of B cell–intrinsic TLR signaling. Thus, innate signals have the capacity to enhance TI-2 antibody responses by promoting participation of FO B cells, which then elaborate effective IgG anti-pathogen antibodies.

IFN-γ produced by CD8 T cells induces T-bet–dependent and –independent class switching in B cells in responses to alum-precipitated protein vaccine

“…Type I IFNs, for example, have been reported to induce IgG2a in T-bet −/− B cells stimulated with LPS (26). The existence of such a Type I IFN-dependent induction of IgG2a in vivo has been confirmed recently (46). This mechanism is distinct from the high level of IFN-γ-and T-dependent CSR to IgG2a reported in this paper, where T-bet induction is likely to occur through the synergic activation of the B cells via their BCR and IFN-γ receptors.…”

Distinctive TLR7 Signaling, Type I IFN Production, and Attenuated Innate and Adaptive Immune Responses to Yellow Fever Virus in a Primate Reservoir Host

“…More recent support documenting the impact of depressed pDC number or function on the induction and maintenance of CD8 + T cell numbers and function have been obtained from studies of YF-17D infection in rapamycin-treated mice (which results in inhibition of IRF-7-dependent IFN-a production) and VSV-infected mice that had been conditionally depleted of pDCs (30,55). Although less is known about the role of TLRs, DCs, and IFN-a in the generation of long-lived memory B cell responses (56), IFN-a has been shown to enhance primary Ab responses, promote isotype switching, influence relative polarization of the Ab isotype profile, and, together with IL-6, stimulate plasma cell differentiation in mice (57)(58)(59)(60). However, detailed mechanistic studies to better understand the role and mechanisms of potentially important effects of TLR7/9 signaling and IFN-a production on the levels, isotype composition, generation of CD4 + T cell and B cell memory, and in the overall persistence of Ab production following specific infections and immunizations in both humans and nonhuman primates (as well as in other vertebrate species that represent natural hosts for zoonotic infections) are clearly needed.…”

Acute Plasmodium chabaudi Infection Dampens Humoral Responses to a Secondary T-Dependent Antigen but Enhances Responses to a Secondary T-Independent Antigen

“…This suggests that IFN-g produced during P. chabaudi infection is primarily skewing toward an increase in IgG2c but not inhibiting IgG1 because of there being no other significant effect on the production of Ab against secondary Ags following IFN-g depletion. Interestingly, type I IFN previously has been shown to skew follicular B cell Ab responses against TI-2 Ags toward an IgG2c isotype (48). Type I IFN is produced during Plasmodium infection (49) and permits B cells to become responsive to IL-12 and become B effector 1 (Be1) cells (50).…”