Regulation of IgG antibody titers by the amount persisting of immune‐complexed antigen

Abstract

Antigens normally induce an immunoglobulin (Ig)G response which stays at an elevated level for several weeks or months, constituting an important part of the immunological memory. This study investigated factors influencing the level of neutralizing IgG titers against a virus and shows that within the range tested it was independent of the number of initially available and potentially responding T helper and B cells, but was regulated by the amount of specific IgG-immune complexes forming depots of persisting antigen. These findings support the notion that the efficiency of vaccines in inducing long-lasting protective IgG is regulated predominantly by the amount of persisting (and presumably follicular dendritic cell-associated) antigen-antibody complexes.

Persistence of Borna Disease Virus in Naturally Infected Sheep

“…Concurrent with the resolution of the acute infection, virus-specific plasma cells rapidly decline in the spleen and plasma cells appear in the bone marrow, which becomes the major site of long-term high-affinity antibody production (41,43). Plasma cells generated in that late phase of an immune reaction represent a successful humoral immune response, and therefore a regulatory function of antigen in humoral immune responses has been postulated (2,30) in which the generation of long-lived plasma cells in the bone marrow depends on the clearance of antigen. In persistent infections, the continuous presence of antigen probably does not evoke the generation of long-lived plasma cells unless the antigen is eventually cleared (30).…”

Textbook Germinal Centers?

“…FDCs and their bound Ag have also been proposed to play a central role in maintenance of the memory B cell pool, in homeostatic regulation of antipathogen serum Ab levels, and in induction of anamnestic B cell responses (32,(35)(36)(37). A role for persistent Ag in the survival of memory B cells has been rendered unlikely by an elegant experiment conducted by Rajewsky and colleagues (38).…”

“…After memory cells acquired new BCRs in vivo due to induced gene targeting, they continued to persist, despite apparent absence of an exogenous ligand for these BCRs. In contrast, there is experimental support for the idea that FDCs and their bound Ag facilitate the activation and differentiation of memory B cells (15,32,36,37,39). Whether secondary FDCs and the Ag they trap function in the putative GC peripheral tolerance checkpoint remains to be tested.…”

Immune complex–mediated antigen presentation induces tumor immunity

“…Capture of ICs by APCs likely contributes to the characteristic rapid appearance of high-titered antigen-specific IgGs during secondary exposures to antigen (19)(20)(21). This enhancement is due to the trapping, retention, and facilitated uptake of exogenous antigen by cellular complement and FcγRs on APCs and the subsequent intracellular targeting to the endosomal processing pathway for presentation onto membraneexpressed MHC class II molecules (22).…”