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Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine.

Pabst O, Ohl L, Wendland M, Wurbel MA, Kremmer E, Malissen B, Förster R - J. Exp. Med. (2004)

Bottom Line: Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria.In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine.These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.

ABSTRACT
Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

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CCR9 mutant intestines harbor reduced numbers of IgA+ PC. Cryosections through the small intestine of wild-type (A) and CCR9-targeted mice (B) were stained for IgA (red), CD3 (green), and nuclei (blue). Unaltered numbers of IgA− cells were present in the lamina propria of wild-type and CCR9 mutant animals, whereas numbers of IgA+ cells were reduced in CCR9 mutants (C, ***, P < 0.001; data were derived from five wild type and five mutants analyzing 60 villi each).
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fig2: CCR9 mutant intestines harbor reduced numbers of IgA+ PC. Cryosections through the small intestine of wild-type (A) and CCR9-targeted mice (B) were stained for IgA (red), CD3 (green), and nuclei (blue). Unaltered numbers of IgA− cells were present in the lamina propria of wild-type and CCR9 mutant animals, whereas numbers of IgA+ cells were reduced in CCR9 mutants (C, ***, P < 0.001; data were derived from five wild type and five mutants analyzing 60 villi each).

Mentions: Based on these findings, we compared the PC populations of wild-type and CCR9 mutant mice by counting the number of IgA+ PCs on cryosections of the small intestine (Fig. 2, A and B). In this paper, only villi were counted that were cut (judged on the analysis of serial sections) through the core of the villus. In wild-type animals, an average of 20.6 ± 1.2 (mean ± SEM) IgA+ cells per villus section was found. In contrast, in CCR9 mutant mice, the number of PCs per villus section was severely reduced to 11 ± 1.1 (mean ± SEM) cells per villus section (Fig. 2 C). As an internal control, the number of IgA− DAPI+ LPCs was determined on the same sections, revealing that CCR9 deficiency does not affect cell types other than IgA+ PCs in this compartment (Fig. 2 C, 19 ± 0.9 cells vs. 22 ± 1.6 cells). These results could also be confirmed by flow cytometry on permeabilized LPCs using an anti-IgA mAb that revealed a reduction of IgA+ PC numbers by ∼50% in CCR9 mutants (unpublished data).


Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine.

Pabst O, Ohl L, Wendland M, Wurbel MA, Kremmer E, Malissen B, Förster R - J. Exp. Med. (2004)

CCR9 mutant intestines harbor reduced numbers of IgA+ PC. Cryosections through the small intestine of wild-type (A) and CCR9-targeted mice (B) were stained for IgA (red), CD3 (green), and nuclei (blue). Unaltered numbers of IgA− cells were present in the lamina propria of wild-type and CCR9 mutant animals, whereas numbers of IgA+ cells were reduced in CCR9 mutants (C, ***, P < 0.001; data were derived from five wild type and five mutants analyzing 60 villi each).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211800&req=5

fig2: CCR9 mutant intestines harbor reduced numbers of IgA+ PC. Cryosections through the small intestine of wild-type (A) and CCR9-targeted mice (B) were stained for IgA (red), CD3 (green), and nuclei (blue). Unaltered numbers of IgA− cells were present in the lamina propria of wild-type and CCR9 mutant animals, whereas numbers of IgA+ cells were reduced in CCR9 mutants (C, ***, P < 0.001; data were derived from five wild type and five mutants analyzing 60 villi each).
Mentions: Based on these findings, we compared the PC populations of wild-type and CCR9 mutant mice by counting the number of IgA+ PCs on cryosections of the small intestine (Fig. 2, A and B). In this paper, only villi were counted that were cut (judged on the analysis of serial sections) through the core of the villus. In wild-type animals, an average of 20.6 ± 1.2 (mean ± SEM) IgA+ cells per villus section was found. In contrast, in CCR9 mutant mice, the number of PCs per villus section was severely reduced to 11 ± 1.1 (mean ± SEM) cells per villus section (Fig. 2 C). As an internal control, the number of IgA− DAPI+ LPCs was determined on the same sections, revealing that CCR9 deficiency does not affect cell types other than IgA+ PCs in this compartment (Fig. 2 C, 19 ± 0.9 cells vs. 22 ± 1.6 cells). These results could also be confirmed by flow cytometry on permeabilized LPCs using an anti-IgA mAb that revealed a reduction of IgA+ PC numbers by ∼50% in CCR9 mutants (unpublished data).

Bottom Line: Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria.In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine.These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.

ABSTRACT
Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

Show MeSH