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 mutant PCs show an impaired migration into the small intestine. (A) 16 h after adoptive transfer of BrdU-labeled cells isolated from MLN and PP of wild-type and CCR9 mutant mice, the number of BrdU+ IgA+ cells per villus was determined (*, P < 0.05; data were derived from three recipients of each group analyzing 60 villi each). CCR9 mutant mice show a reduced humoral IgA response. (B) Groups of 10 CCR9 mutants (solid line) and control animals (dashed line) were each gavaged with OVA and CT at 10-d intervals, and serum levels of OVA-specific IgA were measured. In contrast to wild-type animals showing a robust increase of OVA-specific IgA levels, CCR9 mutants barely produced OVA-specific IgAs.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211800&req=5

fig3: CCR9 mutant PCs show an impaired migration into the small intestine. (A) 16 h after adoptive transfer of BrdU-labeled cells isolated from MLN and PP of wild-type and CCR9 mutant mice, the number of BrdU+ IgA+ cells per villus was determined (*, P < 0.05; data were derived from three recipients of each group analyzing 60 villi each). CCR9 mutant mice show a reduced humoral IgA response. (B) Groups of 10 CCR9 mutants (solid line) and control animals (dashed line) were each gavaged with OVA and CT at 10-d intervals, and serum levels of OVA-specific IgA were measured. In contrast to wild-type animals showing a robust increase of OVA-specific IgA levels, CCR9 mutants barely produced OVA-specific IgAs.

Mentions: More than two decades ago, McDermott et al. identified proliferating cells in MLN and PPs, but not in peripheral LN, that were able to migrate into mucosal tissues and give rise to IgA-secreting cells (17). To directly address the function of CCR9 in this process, we labeled proliferating cells using BrdU and isolated them from MLN and PPs of wild-type and CCR9-deficient mice. 108 cells were injected i.v. into wild-type recipients, and after 16 h, the numbers of BrdU+ IgA+ PCs in the small intestine had been determined. Interestingly, PCs from wild-type mice were threefold more efficient in migrating into the small intestine compared with cells derived from CCR9-deficient mice (Fig. 3 A). These results contributed further weight to the idea that CCR9 is required for efficient migration of newly formed PCs into the small intestine.


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 PCs show an impaired migration into the small intestine. (A) 16 h after adoptive transfer of BrdU-labeled cells isolated from MLN and PP of wild-type and CCR9 mutant mice, the number of BrdU+ IgA+ cells per villus was determined (*, P < 0.05; data were derived from three recipients of each group analyzing 60 villi each). CCR9 mutant mice show a reduced humoral IgA response. (B) Groups of 10 CCR9 mutants (solid line) and control animals (dashed line) were each gavaged with OVA and CT at 10-d intervals, and serum levels of OVA-specific IgA were measured. In contrast to wild-type animals showing a robust increase of OVA-specific IgA levels, CCR9 mutants barely produced OVA-specific IgAs.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: CCR9 mutant PCs show an impaired migration into the small intestine. (A) 16 h after adoptive transfer of BrdU-labeled cells isolated from MLN and PP of wild-type and CCR9 mutant mice, the number of BrdU+ IgA+ cells per villus was determined (*, P < 0.05; data were derived from three recipients of each group analyzing 60 villi each). CCR9 mutant mice show a reduced humoral IgA response. (B) Groups of 10 CCR9 mutants (solid line) and control animals (dashed line) were each gavaged with OVA and CT at 10-d intervals, and serum levels of OVA-specific IgA were measured. In contrast to wild-type animals showing a robust increase of OVA-specific IgA levels, CCR9 mutants barely produced OVA-specific IgAs.
Mentions: More than two decades ago, McDermott et al. identified proliferating cells in MLN and PPs, but not in peripheral LN, that were able to migrate into mucosal tissues and give rise to IgA-secreting cells (17). To directly address the function of CCR9 in this process, we labeled proliferating cells using BrdU and isolated them from MLN and PPs of wild-type and CCR9-deficient mice. 108 cells were injected i.v. into wild-type recipients, and after 16 h, the numbers of BrdU+ IgA+ PCs in the small intestine had been determined. Interestingly, PCs from wild-type mice were threefold more efficient in migrating into the small intestine compared with cells derived from CCR9-deficient mice (Fig. 3 A). These results contributed further weight to the idea that CCR9 is required for efficient migration of newly formed PCs into the small intestine.

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