Antibody‐Mediated Regulation of the Immune Response

Abstract

Antibodies administered in vivo together with the antigen they are specific for can regulate the immune response to that antigen. This phenomenon is called antibody‐mediated feedback regulation and has been known for over 100 years. Both passively administered and actively produced antibodies exert immunoregulatory functions. Feedback regulation can be either positive or negative, resulting in >1000‐fold enhancement or >99% suppression of the specific antibody response. Usually, the response to the entire antigen is up‐ or downregulated, regardless of which epitope the regulating antibody recognizes. IgG of all isotypes can suppress responses to large particulate antigens like erythrocytes, a phenomenon used clinically in Rhesus prophylaxis. IgG suppression works in mice lacking the known Fc‐γ receptors (FcγR) and a likely mechanism of action is epitope masking. IgG1, IgG2a and IgG2b administered together with soluble protein antigens will enhance antibody and CD4+ T‐cell responses via activating FcγR, probably via increased antigen presentation by dendritic cells. IgG3 as well as IgM also enhance antibody responses but their effects are dependent on their ability to activate complement. A possible mechanism is increased B‐cell activation caused by immune complexes co‐crosslinking the B‐cell receptor with the complement‐receptor 2/CD19 receptor complex, known to lower the threshold for B‐cell activation. IgE‐antibodies enhance antibody and CD4+ T‐cell responses to small soluble proteins. This effect is entirely dependent on the low‐affinity receptor for IgE, CD23, the mechanism probably being increased antigen presentation by CD23+ B cells.

CD23-Bound IgE Augments and Dominates Recall Responses through Human Naive B Cells

“…The activation of Agspecific T cells allows for subsequent enhancement of cognate B and T cells to cross-talk and expand. This immunostimulatory effect of CD23-bound IgE is similar to a strong adjuvant and is Ag-specific in mice (11).…”

Innate Immunity Mediates Follicular Transport of Particulate but Not Soluble Protein Antigen

“…Specific Abs have a profound influence on Ab responses (40,41). Protein Ag in the form of ICs with IgM Abs is typically more potent than free Ag in promoting Ab responses (40).…”

“…With IgG Abs, this enhancement was mainly observed with soluble protein Ags, whereas responses against particulate Ags were suppressed (41). This dual effect was dependent on the nature of the Ag, as the same anti-hapten Ab was able to enhance or suppress Ab responses when the hapten was conjugated to a soluble protein or particulate Ag, respectively (42).…”

Circulating specific antibodies enhance systemic cross‐priming by delivery of complexed antigen to dendritic cells in vivo

“…Enhanced specific T-cell responses have been observed after treatment with Mucin 1 [5] and HER2/neu- [6] specific antibodies in humans and after injection of neu-specific antibodies in mice that received a neu-expressing whole cell vaccine [7]. It is well established that antibodies administered in vivo together with their specific antigen can regulate the antigen-specific immune response via antibody-mediated feedback regulation [8]. Although it has been shown that IgG can enhance antibody responses and CD4 + T-cell responses via this process [9], enhancement of CD8 + T-cell responses by antibodies remains poorly understood.…”