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The Extracellular Domains of IgG1 and T Cell-Derived IL-4/IL-13 Are Critical for the Polyclonal Memory IgE Response In Vivo.

Turqueti-Neves A, Otte M, Schwartz C, Schmitt ME, Lindner C, Pabst O, Yu P, Voehringer D - PLoS Biol. (2015)

Bottom Line: The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells.Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells.Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

ABSTRACT
IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders.

No MeSH data available.


Related in: MedlinePlus

IgE+ and IgG1+ PCs increase in numbers in different organs after secondary N. brasiliensis infection.Spleen (SP), pooled mediastinal, and mesenteric LN, lung, and bone marrow (BM) of BALB/c mice were collected 13 d or 10 d after primary and secondary N. brasiliensis infection, respectively. (A) Representative plots show the percentage of PCs (B220–CD138+) from blasts (FSChiSSChi) after primary (upper plots) and secondary (lower plots) N. brasiliensis infection gated as indicated in S10 Fig. Bar graph shows the average percentage of PCs in indicated tissues. (B–E) Bar graphs show the mean percentage of IgG1+ PCs (B), total IgG1+ PCs (C), percentage of IgE+ PC (D) and total IgE+ PC (E) in indicated tissues using the PC gate shown in Fig 5A and intracellular staining for IgG1 and IgE as shown in S11 Fig. Data show the mean + SEM from three independent experiments and at least six mice. *p < 0.05, **p < 0.005, ***p < 0.001 by Student’s t test.
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pbio.1002290.g005: IgE+ and IgG1+ PCs increase in numbers in different organs after secondary N. brasiliensis infection.Spleen (SP), pooled mediastinal, and mesenteric LN, lung, and bone marrow (BM) of BALB/c mice were collected 13 d or 10 d after primary and secondary N. brasiliensis infection, respectively. (A) Representative plots show the percentage of PCs (B220–CD138+) from blasts (FSChiSSChi) after primary (upper plots) and secondary (lower plots) N. brasiliensis infection gated as indicated in S10 Fig. Bar graph shows the average percentage of PCs in indicated tissues. (B–E) Bar graphs show the mean percentage of IgG1+ PCs (B), total IgG1+ PCs (C), percentage of IgE+ PC (D) and total IgE+ PC (E) in indicated tissues using the PC gate shown in Fig 5A and intracellular staining for IgG1 and IgE as shown in S11 Fig. Data show the mean + SEM from three independent experiments and at least six mice. *p < 0.05, **p < 0.005, ***p < 0.001 by Student’s t test.

Mentions: Next, we investigated the distribution of IgE- and IgG1-secreting PCs in different tissues after the first and second N. brasiliensis infection. At day 13 after primary infection, the peak of the humoral response, PCs could be found mainly in the draining LN and spleen of infected mice (Fig 5A). After secondary infection, the total number of PCs mainly increased in the LN and to a lesser extent in lung, spleen, and bone marrow (Fig 5A). IgE+ and IgG1+ PCs were found in the spleen and LN of primary infected mice, and in the memory response they became much more abundant in these organs, whereas IgE+ and IgG1+ PCs in the bone marrow and lung remained relatively scarce, although their numbers increased during the secondary response (Fig 5B–5E).


The Extracellular Domains of IgG1 and T Cell-Derived IL-4/IL-13 Are Critical for the Polyclonal Memory IgE Response In Vivo.

Turqueti-Neves A, Otte M, Schwartz C, Schmitt ME, Lindner C, Pabst O, Yu P, Voehringer D - PLoS Biol. (2015)

IgE+ and IgG1+ PCs increase in numbers in different organs after secondary N. brasiliensis infection.Spleen (SP), pooled mediastinal, and mesenteric LN, lung, and bone marrow (BM) of BALB/c mice were collected 13 d or 10 d after primary and secondary N. brasiliensis infection, respectively. (A) Representative plots show the percentage of PCs (B220–CD138+) from blasts (FSChiSSChi) after primary (upper plots) and secondary (lower plots) N. brasiliensis infection gated as indicated in S10 Fig. Bar graph shows the average percentage of PCs in indicated tissues. (B–E) Bar graphs show the mean percentage of IgG1+ PCs (B), total IgG1+ PCs (C), percentage of IgE+ PC (D) and total IgE+ PC (E) in indicated tissues using the PC gate shown in Fig 5A and intracellular staining for IgG1 and IgE as shown in S11 Fig. Data show the mean + SEM from three independent experiments and at least six mice. *p < 0.05, **p < 0.005, ***p < 0.001 by Student’s t test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4629909&req=5

pbio.1002290.g005: IgE+ and IgG1+ PCs increase in numbers in different organs after secondary N. brasiliensis infection.Spleen (SP), pooled mediastinal, and mesenteric LN, lung, and bone marrow (BM) of BALB/c mice were collected 13 d or 10 d after primary and secondary N. brasiliensis infection, respectively. (A) Representative plots show the percentage of PCs (B220–CD138+) from blasts (FSChiSSChi) after primary (upper plots) and secondary (lower plots) N. brasiliensis infection gated as indicated in S10 Fig. Bar graph shows the average percentage of PCs in indicated tissues. (B–E) Bar graphs show the mean percentage of IgG1+ PCs (B), total IgG1+ PCs (C), percentage of IgE+ PC (D) and total IgE+ PC (E) in indicated tissues using the PC gate shown in Fig 5A and intracellular staining for IgG1 and IgE as shown in S11 Fig. Data show the mean + SEM from three independent experiments and at least six mice. *p < 0.05, **p < 0.005, ***p < 0.001 by Student’s t test.
Mentions: Next, we investigated the distribution of IgE- and IgG1-secreting PCs in different tissues after the first and second N. brasiliensis infection. At day 13 after primary infection, the peak of the humoral response, PCs could be found mainly in the draining LN and spleen of infected mice (Fig 5A). After secondary infection, the total number of PCs mainly increased in the LN and to a lesser extent in lung, spleen, and bone marrow (Fig 5A). IgE+ and IgG1+ PCs were found in the spleen and LN of primary infected mice, and in the memory response they became much more abundant in these organs, whereas IgE+ and IgG1+ PCs in the bone marrow and lung remained relatively scarce, although their numbers increased during the secondary response (Fig 5B–5E).

Bottom Line: The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells.Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells.Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

ABSTRACT
IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders.

No MeSH data available.


Related in: MedlinePlus