Limits...
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.

Show MeSH
CCR9 is expressed on all IgA+ PCs in MLN but on few lamina propria PCs. (A–C) Cells isolated from thymus (A) and small intestinal lamina propria (B and C) of wild-type mice (solid line) and CCR9-deficient animals (dashed line) were stained using a CCR9-specific monoclonal antibody or an isotype control (shaded area). The histograms shown in B were obtained by gating on small LPCs, whereas data shown in C were obtained from large LPCs. (D–F) Three color immunohistology. Sections of MLN (D) and small intestine (E and F) from wild-type mice were stained with anti-CCR9 (D′ and E′, red) or anti-CXCR4 (F′, red). Sections were further stained with anti-IgA (D–F, green) and anti-CD3 (D'–F′, blue). The three colors obtained from single sections have been separated as depicted. Arrows indicate the position of IgA+ PCs.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211800&req=5

fig1: CCR9 is expressed on all IgA+ PCs in MLN but on few lamina propria PCs. (A–C) Cells isolated from thymus (A) and small intestinal lamina propria (B and C) of wild-type mice (solid line) and CCR9-deficient animals (dashed line) were stained using a CCR9-specific monoclonal antibody or an isotype control (shaded area). The histograms shown in B were obtained by gating on small LPCs, whereas data shown in C were obtained from large LPCs. (D–F) Three color immunohistology. Sections of MLN (D) and small intestine (E and F) from wild-type mice were stained with anti-CCR9 (D′ and E′, red) or anti-CXCR4 (F′, red). Sections were further stained with anti-IgA (D–F, green) and anti-CD3 (D'–F′, blue). The three colors obtained from single sections have been separated as depicted. Arrows indicate the position of IgA+ PCs.

Mentions: It has been suggested that the interaction of CCL25 with CCR9 might play an important role in the establishment of an IgA+ PC pool in the small intestine. Therefore, we characterized the expression of CCR9 on PCs in different organs with a newly generated monoclonal antibody against CCR9. The antibody displayed high levels of CCR9 on wild-type thymocytes but not on thymocytes derived from CCR9-deficient mice (Fig. 1 A).


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 is expressed on all IgA+ PCs in MLN but on few lamina propria PCs. (A–C) Cells isolated from thymus (A) and small intestinal lamina propria (B and C) of wild-type mice (solid line) and CCR9-deficient animals (dashed line) were stained using a CCR9-specific monoclonal antibody or an isotype control (shaded area). The histograms shown in B were obtained by gating on small LPCs, whereas data shown in C were obtained from large LPCs. (D–F) Three color immunohistology. Sections of MLN (D) and small intestine (E and F) from wild-type mice were stained with anti-CCR9 (D′ and E′, red) or anti-CXCR4 (F′, red). Sections were further stained with anti-IgA (D–F, green) and anti-CD3 (D'–F′, blue). The three colors obtained from single sections have been separated as depicted. Arrows indicate the position of IgA+ PCs.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: CCR9 is expressed on all IgA+ PCs in MLN but on few lamina propria PCs. (A–C) Cells isolated from thymus (A) and small intestinal lamina propria (B and C) of wild-type mice (solid line) and CCR9-deficient animals (dashed line) were stained using a CCR9-specific monoclonal antibody or an isotype control (shaded area). The histograms shown in B were obtained by gating on small LPCs, whereas data shown in C were obtained from large LPCs. (D–F) Three color immunohistology. Sections of MLN (D) and small intestine (E and F) from wild-type mice were stained with anti-CCR9 (D′ and E′, red) or anti-CXCR4 (F′, red). Sections were further stained with anti-IgA (D–F, green) and anti-CD3 (D'–F′, blue). The three colors obtained from single sections have been separated as depicted. Arrows indicate the position of IgA+ PCs.
Mentions: It has been suggested that the interaction of CCL25 with CCR9 might play an important role in the establishment of an IgA+ PC pool in the small intestine. Therefore, we characterized the expression of CCR9 on PCs in different organs with a newly generated monoclonal antibody against CCR9. The antibody displayed high levels of CCR9 on wild-type thymocytes but not on thymocytes derived from CCR9-deficient mice (Fig. 1 A).

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