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IgG1 Immune Complexes Inhibit Naïve T Cell Proliferation but Stimulate a Subset of Their Progeny

ABSTRACT: We examined the effects of well-defined, soluble IgG1 immune complexes on the phenotypes of human peripheral naive CD8+ T cells. We demonstrate that IgG1-ICs inhibit the proliferation and differentiation of one subset of naïve T cells but stimulate the division of another naïve-like subset. We utilize RNA-Seq to characterize the inhibited and stimulated T cell subsets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166445 | GEO | 2021/06/26

REPOSITORIES: GEO

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IgG1 Immune Complexes Inhibit Naïve T Cell Proliferation but Stimulate a Subset of Their Progeny

Project description:IgG1 Immune Complexes Inhibit Naïve T Cell Proliferation but Stimulate a Subset of Their Progeny

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Expression data from IgE+ and IgG1+ B lymphocytes in mice infected with Nippostrongylus brasiliensis

Project description:The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE cells in these memory responses is particularly unclear. IgE B-cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B-cell receptor function and increased apoptosis. IgE GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B-cell differentiation fates: direct switching generates IgE GC cells, whereas sequential switching gives rise to IgE plasma cells. We propose a comprehensive model for the generation and memory of IgE responses. The purpose of this analysis was to: 1) identify expression differences between IgE and IgG1 B lymphocytes, 2) identify GC Dark Zone (DZ) and Light Zone (LZ) signatures of IgG1 GC cells. For that purpose, we compared in one experiment the gene expression patterns of IgE germinal center (GC) cells, IgG1 GC cells, IgE plasma cells (PC), IgG1 PC and naïve cells. In a second experiment, we compared the expression of IgG1 DZ GC cells with that of IgG1 LZ GC cells. Triplicates obtained from independent sorting experiments were used for all samples except two (IgG1 PC=2 samples; IgE PC=4 samples). Each sample was obtained from a pool of three individual mice. The mice used in the experiment were CeGFP BALB/c mice infected with the parasite N. brasiliensis. CeGFP mice carry an IRES-GFP KI cassette in the 3'UTR of membrane IgE. In these mice, GFP expression marks IgE cells, and a population of IgG1 cells with a rearrangement to Cepsilon in the non-productive (VDJ negative) IgH chromosome.

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