IgG1 memory B cells keep the memory of IgE responses

Abstract

The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80+CD73+ and CD80−CD73−, contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80+CD73+ high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.

Management of allergy transfer upon solid organ transplantation

“…LiverR1 received an extended liver graft and eventually increased number of passenger leukocytes, but on the other hand LiverSplitR2 has never been exposed to peanut before peanut‐specific IgE levels turned negative. Thus, early exposure to allergen after SOT may lead to expansion of IgE‐Bcs, or alternatively switch from IgG1‐MBcs into IgE‐producing cells (Figure ).…”

Regulation of IgE by T follicular helper cells

“…found a convergent pattern of mutations in the IgE antibodies from unrelated peanut‐allergic patients, suggesting that a common stepwise mutational pathway leads to the generation of high‐affinity IgE in allergic individuals . Observations from patients are also supported by findings in murine models of allergic sensitization in which only high‐affinity IgE induces anaphylaxis …”

“…How then is affinity‐matured IgE made? One mechanism that has been demonstrated is sequential switching to IgE via IgG . When IgM B cells switch to IgE B cells, the process is called direct switching.…”

“…How then are life‐long humoral IgE responses maintained? Recent data suggest that IgG1 memory B cells, upon re‐exposure to antigen, can differentiate into IgE PCs to maintain humoral IgE . Thus, for both affinity maturation and maintenance of the IgE response, IgG B cells are a key intermediary.…”

“…21 Observations from patients are also supported by findings in murine models of allergic sensitization in which only high-affinity IgE induces anaphylaxis. 8,15,16,24 Why is high-affinity IgE more adept at inducing anaphylaxis? Elegant signaling experiments have demonstrated that even though all IgE antibodies bind by their Fc region to the high-affinity IgE receptor, Fc RI, the signaling downstream of Fc RI differs depending on whether cross-linking is mediated by high-affinity versus low-affinity antigen-binding fragment (Fab) of IgE, leading to qualitatively distinct outcomes.…”